Genomes and Genes
Summary: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
Publications309 found, 100 shown here
- Glucuronidation of dihydroartemisinin in vivo and by human liver microsomes and expressed UDP-glucuronosyltransferasesKenneth F Ilett
Department of Pharmacology, University of Western Australia, Crawley, Western Australia
Drug Metab Dispos 30:1005-12. 2002..and metabolites were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Human liver microsomes were incubated with [12-(3)H]DHA and cofactors for either glucuronidation or cytochrome P450-catalyzed ..
- Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomesKyoung Ah Kim
Research Group of Pain and Neuroscience, East West Medical Research Institute, Kyung Hee University, 1 Hoegidong, Dongdaemoongu, Seoul, 130 701, South Korea
Life Sci 74:2769-79. 2004..were tested for their ability to modulate the activities of several cytochrome P450 (CYP) enzymes using human liver microsomes. OA competitively inhibited CYP1A2-catalyzed phenacetin O-deethylation and CYP3A4-catalyzed midazolam 1-..
- In vitro metabolism of rivaroxaban, an oral, direct factor Xa inhibitor, in liver microsomes and hepatocytes of rats, dogs, and humansD Lang
Bayer HealthCare AG, Global Drug Discovery, DMPK Drug Metabolism, Building 466, Aprather Weg 18a, D 42096 Wuppertal, Germany
Drug Metab Dispos 37:1046-55. 2009..14)C]Rivaroxaban was incubated with liver microsomes and hepatocytes of rats, dogs, and humans...
- Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenaseJun Gu
Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, New York 12201, USA
J Biol Chem 278:25895-901. 2003..The Alb-Cre/Cprlox mouse represents a unique model for studying the in vivo function of hepatic HO and microsomal CYP-dependent pathways in the biotransformation of endogenous and xenobiotic compounds...
- Regio- and stereospecific N-glucuronidation of medetomidine: the differences between UDP glucuronosyltransferase (UGT) 1A4 and UGT2B10 account for the complex kinetics of human liver microsomesSanna Kaivosaari
Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P O Box 56 Viikinkaari 5, 00014 University of Helsinki, Finland
Drug Metab Dispos 36:1529-37. 2008..Studying medetomidine glucuronidation by human liver microsomes (HLMs) and recombinant UDP glucuronosyltransferase (UGT) 1A4 indicated that another human UGT plays a major ..
- Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6Zeruesenay Desta
Indiana University School of Medicine, Department of Medicine Division of Clinical Pharmacology, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
J Pharmacol Exp Ther 310:1062-75. 2004We performed comprehensive kinetic, inhibition, and correlation analyses in human liver microsomes and experiments in expressed human cytochromes P450 (P450s) to identify primary and secondary metabolic routes of tamoxifen (TAM) and the ..
- Purification and characterization of a neutral, bile salt-independent retinyl ester hydrolase from rat liver microsomes. Relationship To rat carboxylesterase ES-2G Sun
Department of Biochemistry, Medical College of Pennsylvania Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA
J Biol Chem 272:24488-93. 1997..With retinyl palmitate as substrate, the enzyme had a pH optimum of 7 and showed apparent saturation kinetics, with half-maximal activity achieved at substrate concentrations (Km) of approximately 70 microM...
- Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomesT K Chang
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
Cancer Res 53:5629-37. 1993..variation (4-9-fold) was observed in the hydroxylation of these oxazaphosphorines by a panel of 12 human liver microsomes, and a significant correlation was obtained between these 2 activities (r = 0.85, P < 0.001)...
- The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytesAndrew Parkinson
XenoTech, LLC, Lenexa, KS 66219, USA
Toxicol Appl Pharmacol 199:193-209. 2004We have measured cytochrome P450 (CYP) activity in nearly 150 samples of human liver microsomes and 64 samples of cryopreserved human hepatocytes, and we have performed induction studies in over 90 preparations of cultured human ..
- Identification, expression, and purification of a pyrethroid-hydrolyzing carboxylesterase from mouse liver microsomesJeanette E Stok
Department of Entomology and University of California Davis Cancer Research Center, University of California, Davis, California 95616, USA
J Biol Chem 279:29863-9. 2004..A pyrethroid-hydrolyzing enzyme was partially purified from mouse liver microsomes using a fluorescent reporter similar in structure to cypermethrin (Shan, G., and Hammock, B. D. (2001) Anal...
- Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolitesXue Jun Zhao
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Xenobiotica 32:863-78. 2002..and 7-ethoxyresorufin as a substrate of CYP1B1 were examined in catalytic assays carried out using human liver microsomes and cDNA-expression systems. 2...
- Antioxidant properties of Indian medicinal plantsHemant R Jadhav
Department of Natural Products, National Institute of Pharmaceutical Education and Research NIPER, Sector 67, S A S Nagar 160 062 Punjab, India
Phytother Res 16:771-3. 2002..The selective pigment removal from the extracts led to an increase in free radical scavenging activity and a decrease in inhibition of lipid peroxidation...
- 2'-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: formation of a lung carcinogen precursorS S Hecht
University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
Proc Natl Acad Sci U S A 97:12493-7. 2000..The rate was 11% of that of cotinine production. Incubation of human liver microsomes with nicotine gave keto acid by using aminoketone as an intermediate; keto acid was not formed from cotinine...
- CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomesJacqueline Ramirez
University of Chicago, Department of Medicine, Section of Hematology Oncology, 5841 S Maryland Avenue, MC2115, Chicago, IL 60637, USA
Drug Metab Dispos 32:930-6. 2004..studies included 1) screening 16 expressed P450s for normeperidine formation, 2) kinetic experiments on human liver microsomes and candidate P450s, and 3) correlation and inhibition experiments using human hepatic microsomes...
- Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomesJi Young Park
Department of Pharmacology, Gachon Medical School, Incheon, Korea
Antimicrob Agents Chemother 47:3464-9. 2003The inhibitory effect of chloramphenicol on human cytochrome P450 (CYP) isoforms was evaluated with human liver microsomes and cDNA-expressed CYPs...
- Potential beneficial metabolic interactions between tamoxifen and isoflavones via cytochrome P450-mediated pathways in female rat liver microsomesJun Chen
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington 99164, USA
Pharm Res 21:2095-104. 2004..This study aims to evaluate a cytochrome P450-based tamoxifen-isoflavone interaction and to determine the mechanisms responsible for inhibitory effects of isoflavones (e.g., genistein) on the formation of alpha-hydroxytamoxifen...
- Fluorescence-based assays for screening nine cytochrome P450 (P450) activities in intact cells expressing individual human P450 enzymesM Teresa Donato
Unidad de Hepatologia Experimental, Centro de Investigacion, Hospital Universitario La Fe, Avda Campanar 21, 46009, Valencia, Spain
Drug Metab Dispos 32:699-706. 2004..in intact P450-expressing cells and those obtained using the high-performance liquid chromatography-based selective assays in the same cells, in primary human hepatocytes or in human liver microsomes, a fairly good agreement was found.
- Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomesA D Rodrigues
Drug Metabolism Department, Merck Research Laboratories, West Point, PA 19486, USA
Biochem Pharmacol 57:465-80. 1999..g. immunoquantitated levels of each CYP form in native liver microsomes), it is now possible to carry out in vitro "CYP reaction phenotyping" in an integrated manner...
- The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liverJanet K Coller
Dr Margarete Fischer Bosch Institut für Klinische Pharmakologie, Auerbachstrasse 112, D 70376 Stuttgart, Germany
Br J Clin Pharmacol 54:157-67. 2002....
- Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearance and daily doseR Scott Obach
Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
Chem Res Toxicol 21:1814-22. 2008..and nine nonhepatotoxins in humans) were assessed for in vitro covalent binding in NADPH-supplemented human liver microsomes. Of the two sets of nine drugs, seven in each set were shown to undergo some degree of covalent binding...
- N-glucuronidation of trans-3'-hydroxycotinine by human liver microsomesGwendolyn E Kuehl
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA
Chem Res Toxicol 16:1502-6. 2003..We report here that human liver microsomes catalyze both the N-glucuronidation and the O-glucuronidation of trans-3'-hydroxycotinine...
- Glucuronidation of etoposide in human liver microsomes is specifically catalyzed by UDP-glucuronosyltransferase 1A1Yuichiro Watanabe
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan
Drug Metab Dispos 31:589-95. 2003A metabolite formed by incubation of human liver microsomes, etoposide, and UDP-glucuronic acid was identified as etoposide glucuronide by liquid chromatography-tandem mass spectrometry analysis...
- Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoformsM H Court
Molecular Pharmacogenetics, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
J Pharmacol Exp Ther 299:998-1006. 2001..was to identify the relevant UDP-glucuronosyltransferase (UGT) isoforms mediating APAP-UGT activity in human liver microsomes (HLMs)...
- N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferasesGwendolyn E Kuehl
University of Minnesota Cancer Center, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, Minnesota 55455, USA
Drug Metab Dispos 31:1361-8. 2003..Both nicotine and cotinine undergo N-glucuronidation. Human liver microsomes have been shown to catalyze the formation of these N-glucuronides...
- In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by human liver microsomesK Takahashi
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
J Clin Pharm Ther 28:319-27. 2003..Although it is well known that drug-drug interactions may lead to toxicity and therapeutic failure, little is known about the incidence and consequences of herb-drug interactions in patients receiving Kampo medicines...
- Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomesToshifumi Shiraga
Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Osaka, Japan
Biol Pharm Bull 28:124-9. 2005..In the present study, the cytochrome P450 (P450) enzymes responsible for FK228 metabolism in human liver microsomes were investigated...
- Characterization of new bisphenol a metabolites produced by CD1 mice liver microsomes and S9 fractionsJean Philippe Jaeg
Institut National de la Recherche Agronomique, Unité Mixte de Recherche Xénobiotiques, Toulouse, France
J Agric Food Chem 52:4935-42. 2004..Most of these metabolites apparently share a common metabolic pathway, for which considerable evidence supports the hypothesis of the production of a reactive intermediate, and also helps explain BPA cytotoxicity...
- Identification of radicals formed in the reaction mixtures of rat liver microsomes with ADP, Fe3+ and NADPH using HPLC EPR and HPLC EPR MSKatsuyuki Minakata
Department of Chemistry, Wakayama Medical University, 811 1 Kimiidera, Wakayama 641 8509, Japan
J Biochem 142:73-8. 2007The reaction of rat liver microsomes with Fe(3+), ADP and NADPH was examined using EPR, HPLC-EPR and HPLC-EPR-MS combined use of spin trapping technique. A prominent EPR spectrum (alpha(N) = 1.58 mT and alpha(H)beta = 0...
- Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomesYoussef Hijazi
Universite Claude Bernard Lyon 1, Département de Pharmacie Clinique de Pharmacocinétique et d Evaluation du Médicament and Hôpital Neuro Cardiologique, Laboratoire de Dosage des Médicaments, Lyon Cedex, France
Drug Metab Dispos 30:853-8. 2002..In the present study, we investigated the metabolism of ketamine in human liver microsomes at clinically relevant concentrations...
- Genotype-phenotype correlation between the polymorphic UGT2B17 gene deletion and NNAL glucuronidation activities in human liver microsomesPhilip Lazarus
Department of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA
Pharmacogenet Genomics 15:769-78. 2005..by UGT2B17 genotype, a significant or near-significant decrease in NNAL-O-Gluc formation was observed in liver microsomes from individuals who were either heterozygous [(+/0), P=0.07] or homozygous [(0/0), P=0...
- Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomesLeah M Hesse
Clinical Pharmacology Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
Pharmacogenetics 14:225-38. 2004..In conclusion, the results of this study indicate that interindividual variability in bupropion hydroxylation is a consequence of interactions between environmental and genetic influences on CYP2B6 gene function...
- Scaling factors for the extrapolation of in vivo metabolic drug clearance from in vitro data: reaching a consensus on values of human microsomal protein and hepatocellularity per gram of liverZoe E Barter
Academic Unit of Clinical Pharmacology, University of Sheffield, Floor M, The Royal Hallamshire Hospital, Sheffield S10 2JF, UK
Curr Drug Metab 8:33-45. 2007..In the meantime, we recommend that the estimates (and their variances) from the current meta-analysis be used when predicting in vivo kinetic parameters from in vitro data...
- Metabolism of 3-methylindole by porcine liver microsomes: responsible cytochrome P450 enzymesG J Diaz
Department of Animal and Poultry Science, University of Guelph, Ontario, Canada
Toxicol Sci 55:284-92. 2000..The results of the present study indicate that the CYP2A6 porcine ortholog plays an important role in the metabolism of 3MI and that measurement of CYP2A6 levels and/or activity could be a useful marker for 3MI-induced boar taint...
- Biotransformation of N-ethyl-N-(2-hydroxyethyl)perfluorooctanesulfonamide by rat liver microsomes, cytosol, and slices and by expressed rat and human cytochromes P450Lin Xu
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14624, USA
Chem Res Toxicol 17:767-75. 2004..N-EtFOSE and several putative metabolites were incubated with liver microsomes and cytosol and with liver slices from male Sprague-Dawley rats...
- Solubilization, purification and characterization of lysoplasmalogen alkenylhydrolase (lysoplasmalogenase) from rat liver microsomesM Jurkowitz-Alexander
Department of Physiological Chemistry, Ohio State University, Columbus 43210
Biochim Biophys Acta 1002:203-12. 1989..3.2.2; EC 126.96.36.199) has been purified 200-fold to a specific activity of 8.0 mumol/min per mg from rat liver microsomes with 51% of the activity recovered...
- Developmental exposure to brominated diphenyl ethers results in thyroid hormone disruptionTong Zhou
Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA
Toxicol Sci 66:105-16. 2002..8-fold; UDPGT = 0.5-fold). These data support the conclusion that DE-71 is an endocrine disrupter in rats during development...
- The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactionsR Scott Obach
Pfizer Global Research and Development, Groton Laboratories, MS4088, Groton, CT 06340, USA
J Pharmacol Exp Ther 316:336-48. 2006..DDI) was examined for over 40 drugs using seven human P450-selective marker activities in pooled human liver microsomes. These data were combined with other parameters (systemic C(max), estimated hepatic inlet C(max), fraction ..
- Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphismMichael H Court
Comparative and Molecular Pharmacogenetics Laboratory, Tufts University, Boston, MA 02111, USA
Drug Metab Dispos 31:1125-33. 2003..3'-azido-3'-deoxythymidine (AZT), morphine, and codeine], were evaluated using recombinant UGTs and human liver microsomes (HLMs; n = 54)...
- Metabolism and metabolic inhibition of gambogic acid in rat liver microsomesYi Tong Liu
Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
Acta Pharmacol Sin 27:1253-8. 2006To study the metabolism of gambogic acid (GA) and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of GA in rat liver microsomes in vitro.
- Reverse geometrical selectivity in glucuronidation and sulfation of cis- and trans-4-hydroxytamoxifens by human liver UDP-glucuronosyltransferases and sulfotransferasesTakahito Nishiyama
Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432 1 Horinouchi, Hachioji shi, Tokyo 192 0392, Japan
Biochem Pharmacol 63:1817-30. 2002..glucuronidation of cis-HO-TAM, which correlated well with glucuronidation of 4-hydroxybiphenyl by human liver microsomes. However, there was only a slight correlation between the glucuronidation of cis-HO-TAM and trans-HO-TAM or 4-..
- Sex-dependent genetic markers of CYP3A4 expression and activity in human liver microsomesMarkus Schirmer
Georg August University, Department of Clinical Pharmacology, Gottingen, Germany
Pharmacogenomics 8:443-53. 2007..To find genetic markers of the individual cytochrome P450 (CYP)3A expression...
- An evaluation of the cytochrome p450 inhibition potential of lisdexamfetamine in human liver microsomesSuma Krishnan
New River Pharmaceuticals, Blacksburg, VA 24060, USA
Drug Metab Dispos 35:180-4. 2007..was recently analyzed for inhibitory drug-drug interactions with seven major P450 isoforms using pooled human liver microsomes. Probe substrates were used near the K(m) concentration values reported in the literature for CYP1A2 (..
- Inhibition of free radical-induced peroxidation of rat liver microsomes by resveratrol and its analoguesYu Jun Cai
National Laboratory of Applied Organic Chemistry, Lanzhou University, Gansu 730000, Lanzhou, China
Biochim Biophys Acta 1637:31-8. 2003..were synthesized and their antioxidant activity studied for the free radical-induced peroxidation of rat liver microsomes in vitro...
- Metabolic activation of nevirapine in human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4Bo Wen
Drug Metabolism and Pharmacokinetics, M S S3 2 E 218, Roche Palo Alto, Palo Alto, CA 94304, USA
Drug Metab Dispos 37:1557-62. 2009..initiated to determine whether nevirapine undergoes cytochrome P450 (P450)-mediated bioactivation in human liver microsomes to electrophilic intermediates...
- Metabolism of methoxymorpholino-doxorubicin in rat, dog and monkey liver microsomes: comparison with human microsomesD Beulz-Riche
, CHU de la Cavale Blanche, Bd Tanguy Prigent, 29609 Brest Cedex, France
Fundam Clin Pharmacol 15:373-8. 2001..In this study, MMDx in vitro metabolism was compared in rat, dog, monkey and human liver microsomes.When microsomal fractions were incubated with MMDx, 6-8 metabolites were formed depending on the species and ..
- Cytochrome P450-dependent N-dealkylation of L-deprenyl in C57BL mouse liver microsomes: effects of in vivo pretreatment with ethanol, phenobarbital, beta-naphthoflavone and L-deprenylM Valoti
Istituto di Scienze Farmacologiche, Universita degli Studi di Siena, via Piccolomini 170, 53100, Siena, Italy
Eur J Pharmacol 391:199-206. 2000..After preincubation of L-deprenyl with liver microsomes from control or treated mice, the metabolites were analysed by a GLC method. L-deprenyl (10 mg/kg i.p...
- Metabolic stability and determination of cytochrome P450 isoenzymes' contribution to the metabolism of medetomidine in dog liver microsomesMarie Claude Duhamel
Groupe de recherche en pharmacologie animal du Québec GREPAQ, Département de Biomédecine Vétérinaire, Faculte de Medecine Veterinaire, Universite de Montreal, St Hyacinthe, Quebec, Canada
Biomed Chromatogr 24:868-77. 2010..study was to establish the metabolic stability and determine the metabolic pathway of medetomidine in dog liver microsomes. Consequently, Michaelis-Menten parameters (V(max), K(m)), T(1/2) and CL(i) were determined...
- Evidence for multiple glucuronide transporters in rat liver microsomesMiklos Csala
Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland
Biochem Pharmacol 68:1353-62. 2004..liquid chromatography-mass spectrometry, we measured the transport of a variety of beta-D-glucuronides in rat liver microsomes and investigated the substrate specificity of the participating transporter(s) by inhibition studies...
- Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact more than protein bindingCuyue Tang
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486 0004, USA
Drug Metab Dispos 30:648-54. 2002..PHT) to p-hydroxy phenytoin (pHPPH), and tolbutamide (TLB) to 4-hydroxy tolbutamide (hydroxy-TLB), in human liver microsomes was studied in the presence of increasing concentrations (0-4%) of bovine serum albumin (BSA)...
- Inhibitory effects of angiotensin receptor blockers on CYP2C9 activity in human liver microsomesEmi Kamiyama
Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co, Ltd, Tokyo, Japan
Drug Metab Pharmacokinet 22:267-75. 2007..3-300 microM), on the CYP2C9 activity in human liver microsomes using (S)-(-)-warfarin as a typical CYP2C9 substrate...
- Metabolism and metabolic inhibition of cilnidipine in human liver microsomesXiao Quan Liu
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009
Acta Pharmacol Sin 24:263-8. 2003To study the metabolism of cilnidipine and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of cilnidipine in human liver microsomes in vitro.
- Effect of purified saponin mixture from Astragalus corniculatus on enzyme- and non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously hypertensive rats and normotensive ratsR L Simeonova
Laboratory of Drug metabolism and drug toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University, 2 Dunav St, 1000 Sofia, Bulgaria
Phytomedicine 17:346-9. 2010..Fabaceae), on enzyme-induced and non-enzyme-induced lipid peroxidation (LPO), in liver microsomes from spontaneously hypertensive rats (SHRs) - strain Okamoto Aoki, as compared to normotensive Wistar rats (..
- Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomesMitsuo Miyazawa
Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka, Osaka, Japan
Drug Metab Dispos 30:602-7. 2002..and (-)-Limonene enantiomers were incubated with human liver microsomes and the oxidative metabolites thus formed were analyzed using gas chromatography-mass spectrometry...
- Development of an in vivo rat screen model to predict pharmacokinetic interactions of CYP3A4 substratesS V Mandlekar
Pharmaceutical Candidate Optimization, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA
Xenobiotica 37:923-42. 2007..reaction phenotyping was conducted using individual human and rat cDNA-expressed CYP enzymes and human or rat liver microsomes in the presence of ketoconazole...
- Identification of a novel glutathione conjugate of flutamide in incubations with human liver microsomesPing Kang
Pharmacokinetics Dynamics and Metabolism, Pfizer Global Research and Development, San Diego, CA 92121, USA
Drug Metab Dispos 35:1081-8. 2007..Interestingly, the same adduct was formed when flutamide was incubated with human liver microsomes in the presence of GSSG and NADPH...
- Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolitesYoichi Kohno
Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1 2 3, Minami Ku, Hiroshima 734 8551, Japan
Drug Metab Dispos 33:1115-23. 2005When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and trans-4-(4-hydroxyphenyl)-3-buten-2-one (4-OH-PBO), respectively, were formed as ..
- Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomesGwendolyn E Kuehl
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Drug Metab Dispos 33:1027-35. 2005..were determined for expressed UGT Supersomes and compared with parameters determined in pooled human liver microsomes (HLMs)...
- Characterization of protein tyrosine phosphatase activity in rat liver microsomes: suppressive effect of endogenous regucalcin in transgenic ratsYuko Fukaya
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
Int J Mol Med 14:427-32. 2004..protein in intracellular signaling system, in the regulation of protein phosphatase activity in rat liver microsomes was investigated...
- Novel metabolites of buprenorphine detected in human liver microsomes and human urineYan Chang
University of Utah, Center for Human Toxicology, Department of Pharmacology and Toxicology, 417 Wakara Way, Suite 2111, Salt Lake City, UT 84108, USA
Drug Metab Dispos 34:440-8. 2006..M1 and M2) and three hydroxylated norbuprenorphine (M3, M4, and M5) metabolites were produced by human liver microsomes (HLMs), with hydroxylation occurring at the tert-butyl group (M1 and M3) and at unspecified site(s) on the ..
- Expression and activity of cytochromes P450 2E1, 2A, and 2B in the mouse ovary: the effect of 4-vinylcyclohexene and its diepoxide metaboliteEllen A Cannady
University of Arizona, Department of Pharmacology and Toxicology, Tucson, Arizona 85721, USA
Toxicol Sci 73:423-30. 2003..Interestingly, there is high expression of these isoforms in the Int. Thus, the ovary may contribute to ovotoxicity by promoting bioactivation of VCH to the toxic metabolite, VCD...
- Evidence that liver microsomes of human neonates desaturate essential fatty acidsJ P Poisson
Unité de Recherche de Nutrition Cellulaire et Métabolique, Universite de Bourgogne, Faculte des Sciences Mirande, Dijon, France
Biochim Biophys Acta 1167:109-13. 1993..We report the delta 6- and delta 5-desaturase activities detected in human liver microsomes from three neonates who died from associated malformations...
- In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) by liver microsomes from rats, hamsters and guinea pigsC Ohta
Faculty of Nutritional Sciences, Nakamura Gakuen University, Johnan ku, Fukuoka, Japan
Xenobiotica 35:319-30. 2005The metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl (heptaCB) (CB187) was studied using liver microsomes of rats, hamsters and guinea pigs, and the effect of cytochrome P450 (CYP) inducers, phenobarbital (PB) and 3-methylcholanthrene (..
- Predictions of the in vivo clearance of drugs from rate of loss using human liver microsomes for phase I and phase II biotransformationsMichael A Mohutsky
Department of Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
Pharm Res 23:654-62. 2006....
- Deacetylclivorine: a gender-selective metabolite of clivorine formed in female Sprague-Dawley rat liver microsomesGe Lin
Department of Pharmacology, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR
Drug Metab Dispos 35:607-13. 2007..was shown as the predominant pathway ( approximately 16% clivorine metabolism) in female rat liver microsomes and was determined to be mediated by microsomal hydrolase A...
- Selective inhibition of human cytochrome P4502C8 by montelukastRobert L Walsky
Department of Pharmacokinetics, Dynamics, and Drug Metabolism, Pfizer Global Research and Development, Groton Laboratories, Groton, CT 06340, USA
Drug Metab Dispos 33:413-8. 2005..amodiaquine N-deethylase, rosiglitazone N-demethylase, and paclitaxel 6alpha-hydroxylase in human liver microsomes. Inhibition was also observed when the reaction was catalyzed by recombinant heterologously expressed CYP2C8...
- Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomesM H Court
Department of Pharmacology and Experimental Therapeutics, Tufts University, Boston, Massachusetts 02111, USA
Anesthesiology 94:110-9. 2001..The aim of this study was to identify the principal cytochrome P-450 (CYP) isoforms mediating this biotransformation...
- CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime]Michael Zhuo Wang
Division of Molecular Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Drug Metab Dispos 34:1985-94. 2006..We report an in vitro metabolism study to characterize enzymes in human liver microsomes (HLMs) that catalyze the initial O-demethylation of DB289 (M1 formation)...
- Isolation from pig liver microsomes, identification by electrospray tandem mass spectrometry and in vitro immunosuppressive activity of a rapamycin tris-epoxide metaboliteG Lhoest
Department of Pharmaceutical Sciences, UCL, FATC, Brussels, Belgium
J Mass Spectrom 34:28-32. 1999It was demonstrated that rapamycin is metabolized in vitro by pig liver microsomes under the influence of the cytochrome P450-dependent mixed function oxygenase system to a rapamycin tris-epoxide metabolite, as demonstrated by ..
- 4-Aminobiphenyl N-glucuronidation by liver microsomes: optimization of the reaction conditions and characterization of the UDP-glucuronosyltransferase isoformsMustafa Al-Zoughool
McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Canada
J Appl Toxicol 26:524-32. 2006..This is the first report that tried to optimize the incubation conditions for 4-ABP N-glucuronidation and characterized the enzyme kinetic parameters of UGT isoforms catalysing 4-ABP N-glucuronidation...
- Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomesHiroyoshi Nakamura
Division of Pharmacy, Chiba University Hospital, Chuo Ku, Chiba, Japan
Drug Metab Dispos 30:534-40. 2002..study, we investigated the effects of 14 endogenous steroids on the CYP3A4-mediated drug metabolism by human liver microsomes in vitro...
- Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomesKyoung Ah Kim
Department of Pharmacology, Gil Medical Center, Gachon Medical School, 1198 Kuwol dong, 405 760, Incheon, Namdong gu, Korea
Eur J Clin Pharmacol 60:575-81. 2004The purpose of the present study was to elucidate the cytochrome P450 (P450) isoform(s) involved in the metabolism of loperamide (LOP) to N-demethylated LOP (DLOP) in human liver microsomes.
- Oxidative metabolism of monensin in rat liver microsomes and interactions with tiamulin and other chemotherapeutic agents: evidence for the involvement of cytochrome P-450 3A subfamilyC Nebbia
Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Italy
Drug Metab Dispos 27:1039-44. 1999..In liver microsomes from untreated rats (UT) or from rats pretreated, respectively, with ethanol (ETOH), beta-naphthoflavone (..
- Functional reconstitution into liposomes and characterization of the carnitine transporter from rat liver microsomesAnnamaria Tonazzi
National Research Council CNR Institute of Biomembranes and Bioenergetics IBBE, Via Amendola 165 A 70126 Bari, Italy
Biochim Biophys Acta 1758:124-31. 2006The carnitine transporter was solubilized from rat liver microsomes with Triton X-100 and reconstituted into liposomes, after addition of Triton X-114, by removing the detergent from mixed micelles by hydrophobic chromatography on ..
- Prediction of drug clearance by glucuronidation from in vitro data: use of combined cytochrome P450 and UDP-glucuronosyltransferase cofactors in alamethicin-activated human liver microsomesPeter J Kilford
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK
Drug Metab Dispos 37:82-9. 2009..gemfibrozil, ketoprofen, midazolam, naloxone, raloxifene, and zidovudine were determined in pooled human liver microsomes using the substrate depletion approach...
- Inhibition of cytochrome P450 isozymes in rat liver microsomes by polysaccharides derived from Phellinus linteusYun Hee Shon
Department of Pharmacology, College of Medicine and Intractable Disease Research Center, Dongguk University, Kyongju 780 714, Korea
Biotechnol Lett 25:167-72. 2003..of Phellinus linteus inhibited cytochrome P450 (CYP) 1A1, CYP 1A2, CYP 2B1, and CYP 2E1 activities in rat liver microsomes. The polysaccharides from the broth of Phellinus linteus grown with 5% (v/v) mulberry extract had highest ..
- Ethanol oxidation into acetaldehyde by 16 recombinant human cytochrome P450 isoforms: role of CYP2C isoforms in human liver microsomesS Hamitouche
Laboratory of Biochemistry, EA 948, Faculty of Medicine, CS 93837, 29238 Brest Cedex, France
Toxicol Lett 167:221-30. 2006..found between ethanol oxidation and CYP2E1, CYP3A4 and CYP1A2 catalytic activities in a panel of human liver microsomes confirmed the strong implication of these CYPs in ethanol metabolism...
- Metabolic inhibition and kinetics of raloxifene by pharmaceutical excipients in human liver microsomesAe Ra Kim
National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea
Int J Pharm 368:37-44. 2009..of pharmaceutical excipients (PEs) on drug metabolism in uridine diphosphoglucuronic acid-supplemented human liver microsomes. Poorly bioavailable raloxifene was chosen as a model drug...
- Correlation between the UDP-glucuronosyltransferase (UGT1A1) TATAA box polymorphism and carcinogen detoxification phenotype: significantly decreased glucuronidating activity against benzo(a)pyrene-7,8-dihydrodiol(-) in liver microsomes from subjects with Jia Long Fang
Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida, USA
Cancer Epidemiol Biomarkers Prev 13:102-9. 2004..of BPD(-) in humans, we compared UGT1A1 TATAA box genotype with BPD(-) glucuronidating activity in normal liver microsomes. Significant decreases in UGT1A1 protein (P < 0.005) and bilirubin conjugation activity (P < 0...
- In vitro metabolism of leflunomide by mouse and human liver microsomesEric C Y Chan
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543
Drug Metab Lett 1:299-305. 2007..M1 and M2 were proposed to be the hydroxylated alpha-cyanoenol form of A77-1726 and the hydroxylated 5 methyl-isoxazole form of leflunomide, respectively...
- Involvement of multiple UDP-glucuronosyltransferase 1A isoforms in glucuronidation of 5-(4'-hydroxyphenyl)-5-phenylhydantoin in human liver microsomesMiki Nakajima
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan
Drug Metab Dispos 30:1250-6. 2002..In the present study, 4'-HPPH O-glucuronidation in human liver microsomes was investigated...
- Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomesGwendolyn E Kuehl
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 100 Fairview Ave N, Seattle, WA 98109, USA
Drug Metab Dispos 34:199-202. 2006..catalyzing the glucuronidation of salicylic acid using both heterologously expressed enzymes and pooled human liver microsomes (HLMs) and to develop a liquid chromatography-tandem mass spectrometry method to quantify glucuronidation ..
- Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomesG Facciola
Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Huddinge University Hospital, Karolinska Institutet, 14186 Stockholm, Sweden
Eur J Clin Pharmacol 56:881-8. 2001..The present study was carried out to identify the cytochrome P450 enzyme(s) involved in the 6-hydroxylation and O-demethylation of melatonin...
- Role of human liver microsomes in in vitro metabolism of drugs-a reviewSepuri Asha
Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam Women s University, Tirupati, 517 502, Andhra Pradesh, India
Appl Biochem Biotechnol 160:1699-722. 2010..Different approaches are provided and emphasis is placed on the potential of human liver microsomes for drug metabolism and inhibition studies...
- Trans-3'-hydroxycotinine O- and N-glucuronidations in human liver microsomesHiroyuki Yamanaka
Drug Metabolism and Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medical Science, Kanazawa University, Kakuma machi, Kanazawa 920 1192, Japan
Drug Metab Dispos 33:23-30. 2005..Incubation of human liver microsomes with UDP-glucuronic acid produces not only trans-3'-hydroxycotinine O-glucuronide but also N-glucuronide...
- N-glucuronidation of nicotine and cotinine in human: formation of cotinine glucuronide in liver microsomes and lack of catalysis by 10 examined UDP-glucuronosyltransferasesOmar Ghosheh
Drug Metabolism and Drug Disposition Group, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Drug Metab Dispos 30:991-6. 2002..included determination of the kinetics of formation of S(-)-cotinine N1-glucuronide in pooled human liver microsomes and investigation of the UDP-glucuronosyltransferases (UGTs) involved in N-glucuronidation of nicotine ..
- Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomesBertrand Piver
Laboratory of Biochemistry, EA 948, Faculty of Medicine, CS 93837, 29238 Brest Cedex, France
Biochem Pharmacol 68:773-82. 2004..pmol min(-1) mg(-1) protein for piceatannol and 29-161 pmol min(-1) mg(-1) protein for M1 in the 13 human liver microsomes tested...
- Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomesM Baumhakel
Clinical Pharmacology, Institute for Pharmacology, University of Koln, Germany
Int J Clin Pharmacol Ther 39:517-28. 2001..Since these drugs are usually administered in a polychemotherapy regimen, the objective of this study was to examine their inhibitory potency on CYP3A4 with regard to possible mutual drug interactions...
- Investigation into UDP-glucuronosyltransferase (UGT) enzyme kinetics of imidazole- and triazole-containing antifungal drugs in human liver microsomes and recombinant UGT enzymesKarine Bourcier
Pfizer Global R and D, Ramsgate Rd, Sandwich, Kent CT13 9NJ, UK
Drug Metab Dispos 38:923-9. 2010..In this study, evidence for glucuronidation of azole-containing compounds was studied in human liver microsomes (HLM)...
- Inhibitory effect of 5-fluorouracil on human cytochrome P(450) isoforms in human liver microsomesJi Young Park
Department of Pharmacology, Gachon Medical School, 1198 Kuwol dong, Namdong gu, 405 760 Incheon, Korea
Eur J Clin Pharmacol 59:407-9. 2003..The aim of the present study was to elucidate the inhibitory effect of 5-FU on CYP isoforms using human liver microsomes.
- Development of a rapid and sensitive high-performance liquid chromatographic method to determine CYP2D6 phenotype in human liver microsomesBhaskar Rege
VCU School of Pharmacy, MCV Campus, Richmond, VA 23298 0533, USA
Biomed Chromatogr 16:31-40. 2002..to develop a non-LLE based rapid and sensitive HPLC method, to measure dextromethorphan metabolism in human liver microsomes. A solid-phase filtration based reverse-phase HPLC method with fluorescence detection was developed and ..
- Cytochrome P450 enzyme-mediated degradation of Echinacea alkylamides in human liver microsomesA Matthias
MediHerb Research Laboratories, Department of Chemistry, The University of Queensland, Brisbane, QLD 4072, Australia
Chem Biol Interact 155:62-70. 2005..In this study we have investigated the metabolism by human liver microsomes of the alkylamide components from an Echinacea preparation as well as that of pure synthetic alkylamides...
- Biotransformation of brominated flame retardants into potentially endocrine-disrupting metabolites, with special attention to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)Timo Hamers
Institute for Environmental Studies IVM, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Mol Nutr Food Res 52:284-98. 2008..Metabolites were obtained by incubating single-parent compound BFRs with phenobarbital-induced rat liver microsomes. Incubation extracts were tested in seven in vitro bioassays for their potency to compete with thyroxine for ..
- Identification of cytochrome P450 enzymes involved in the metabolism of 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomesD Springer
Department of Experimental and Clinical Toxicology, University of Saarland, Homburg Saar, Germany
Xenobiotica 33:989-98. 2003..its demethylated major metabolite 4'-hydroxy-pyrrolidinopropio-phenone (HO-PPP) was studied in pooled human liver microsomes (HLM) and in cDNA-expressed human hepatic cytochrome P450 (CYP) enzymes. 2...
- Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomesLu Gan
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
Drug Metab Dispos 37:90-6. 2009..CPR and b(5) were measured in human liver microsomes (HLMs) by spectrophotometry and immunoblotting...
- Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomesTakaki Toda
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
Basic Clin Pharmacol Toxicol 105:327-32. 2009..to 5-hydroxy fluvastatin (M-2), 6-hydroxy fluvastatin (M-3) and N-desisopropyl fluvastatin (M-5) in human liver microsomes by primarily CYP2C9...
- Membrane transport of fatty acylcarnitine and free L-carnitine by rat liver microsomesJason M Gooding
Department of Biochemistry and Molecular Biology, University College London, UK
Eur J Biochem 271:954-61. 2004..These findings are relevant to the understanding of processes for the reassembly of triacylglycerols that lipidate very low density lipoprotein particles as part of a hepatic triacylglycerol lipolysis/re-esterification cycle...
- A proteomic method for analysis of CYP450s protein expression changes in carbon tetrachloride induced male rat liver microsomesNuan Jia
Shanghai Key Laboratory for Pharmaceutical Metabolites Research, School of Pharmacy, Second Military Medical University, No 325 Guohe Road, Shanghai 200433, PR China
Toxicology 237:1-11. 2007..21. With this approach, 17 cytochrome P450 proteins were identified and quantified with high confidence. Among them, the expression amount of 2C11, 3A2, and 2 E1 were down-regulated, while that of 2C6, 2B2, and 2B1 were up-regulated...
- A literature review of enzyme kinetic parameters for CYP3A4-mediated metabolic reactions of 113 drugs in human liver microsomes: structure-kinetics relationship assessmentH Z Bu
Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, San Diego, CA 92121, USA
Curr Drug Metab 7:231-49. 2006..parameters (K(m), V(max), and V(max)/K(m)) of 215 CYP3A4-mediated metabolic reactions of 113 drugs in human liver microsomes were obtained from the literature, and lipophilicity values of the 113 drugs were calculated using the ACD/..
- Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysisMing Yao
Department of Biotransformation, Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, NJ 08543, USA
J Pharm Biomed Anal 44:211-23. 2007..S)-mephenytoin for CYP2C19, dextromethorphan for CYP2D6 and midazolam and testosterone for CYP3A4) in human liver microsomes were developed...
- Validation of (-)-N-3-benzyl-phenobarbital as a selective inhibitor of CYP2C19 in human liver microsomesXiaoxin Cai
Department of Drug Metabolism, Merck Research Laboratories, Rahway, New Jersey 07065, USA
Drug Metab Dispos 32:584-6. 2004..To validate the selectivity of NBPB toward CYP2C19 in human liver microsomes, the inhibitory effects on major cytochrome P450 isoform-specific reactions were evaluated in the present ..
- In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomesJ Fang
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Drug Metab Dispos 29:1638-43. 2001..was carried out to elucidate the enzymes responsible for the metabolism of haloperidol (HAL) using human liver microsomes and recombinant human cytochrome P450 isoenzymes...
- Rational Development of Anti-Trypanosoma Cruzi DrugsMichael H Gelb; Fiscal Year: 2013..Follow up studies will test aqueous solubility, stability in liver microsomes, and inhibition of human CYP450 enzymes...
- A Diarylheptanoid Scaffold to Treat TaopathiesChad A Dickey; Fiscal Year: 2013..The eADME studies will include metabolism in mouse and human liver microsomes, human plasma protein binding, water solubility testing, broad receptor and ion channel profiling including ..
- Pharmacokinetics and Metabolism of Oxidized CurcuminClaus Schneider; Fiscal Year: 2013..tissue distribution, and metabolism of the oxidative metabolites of curcumin in the mouse and in human liver microsomes. The following specific aims will be performed: (1) To develop a specific and accurate isotope- dilution ..
- Factors Determining Bisphenol A Disposition in Human InfantsD Gail McCarver; Fiscal Year: 2013..UGT2B15 ontogeny and the developmental changes in BPA metabolism in a large, well-characterized bank of human liver microsomes from donors ranging in age from 8 weeks gestation to 18 years postnatal age...
- PGRMC1: A Regulator of CYP3A ActivityErin G Schuetz; Fiscal Year: 2010..and without expressed PGRMC;(b) CYP3A4/POR supersomes reconstituted with purified PGRMC1;and (c) pooled human liver microsomes in which PGRMC1 activity is decreased with PGRMC1 inhibitory antibodies...
- Development of a novel agent for lung cancer preventionArun Kumar Sharma; Fiscal Year: 2013..Furthermore, to begin establishing the mechanism, we will carry out its metabolism using liver microsomes to establish if p-XS-Asp will cleave into active metabolites p-XSeH and aspirin, and evaluate COX-2-mediated ..
- Bioactivation of PBDEs by Human Cytochrome P-450James R Olson; Fiscal Year: 2013..Interindividua variability in the in vitro metabolism of PBDEs will be assessed utilizing both human liver microsomes, with up to a 100-fold range in the level of CYP2B6 activity, and recombinant polymorphic variants of human ..
- IND-enabling Studies and GMP Scale-up of 18-Methoxycoronaridine hydrochloride(18-Scott Freeman; Fiscal Year: 2013..bacterial reverse mutation, chromosome aberration in human peripheral blood lymphocytes, p450 using human liver microsomes and cardiac action potential duration in rabbit Purkinje fibers and in vivo mouse micronucleus, all of which ..
- Characterization of a Novel Selective Cytochrome P450 3A5 SubstrateMICHAEL DARIN CAMERON; Fiscal Year: 2013..generated using a CYP3A assay measuring testosterone hydroxylation or midazolam hydroxylation by pooled human liver microsomes. While both of these substrates are metabolized by CYP3A4 and CYP3A5, the resulting inhibition constants ..
- In vitro detection of anti-TB liver metabolites in early drug discoveryScott G Franzblau; Fiscal Year: 2013..Enzymatic MGS includes liver microsomes, S9 fractions, recombinant CYP450 enzymes and combinations of these systems and can be used in a one-pot ..
- Drug Discovery for Human African TrypanosomiasisRichard Tidwell; Fiscal Year: 2013..In vitro experiments will be done to assess aqueous solubility, the stability of compounds to metabolism by liver microsomes, and membrane permeability...
- Medications for the Treatment of Alcohol Abuse and Dependence and RelapseLAWRENCE SNELL; Fiscal Year: 2009..DCUKA in blood and tissues;(3) ascertain in vivo oral pharmacokinetics and in vitro metabolism of DCUKA in liver microsomes;and (4) toxicology and safety studies in rats (acute and multiple dose tolerance, genetic toxicity, chronic ..
- Antileishmanial Lead Optimization of QuinazolinesKarl A Werbovetz; Fiscal Year: 2013..and metabolic stability testing for active 2,4-diaminoquinazolines will be performed using mouse and human liver microsomes to inform our synthesis efforts in Aim 1 to enhance oral bioavailability and systemic exposure...
- Advancing lead dipiperidine compound into preclinical developmentMarina Protopopova; Fiscal Year: 2009..We will investigate the pharmacological properties of SQ609: stability evaluation in plasma and liver microsomes and plasma protein binding of SQ609;determination of pharmacokinetic parameters of SQ609 and bioavailability ..
- LEUKOCYTE, ENZYME AND DRUG CHEMILUMINESCENCE STUDIESJEFFREY KANOFSKY; Fiscal Year: 1990..The mechanism of singlet oxygen in liver microsomes supplemented with 13-hydro-peroxylinoleic acid will be determined...
- Nomethiazoles Harnessing GABA and NO mimetic activity for Alzheimer's therapyGregory R J Thatcher; Fiscal Year: 2013..Stability in human/rodent plasma and liver microsomes will be investigated and PK profiles generated for nomethiazole and MZ metabolite in brain and plasma after i...
- MATURATION OF LIVER FOR THE METABOLISM OF BILIRUBINGlenn Gourley; Fiscal Year: 1993..The "activator" peptide of the B-UPDGt will be isolated from the solubilized liver microsomes from the KCI gradient elutions of the initial anion-exchange chromatography of the B-UPDGt...
- ISOLATION OF ELONGATION ENZYMES & SITE OF SYNTHESISDOMINICK CINTI; Fiscal Year: 1991..Recent studies have led us to question the current belief of the existence of several elongation pathways in liver microsomes. Therefore, attempts will be made to substantiate or disprove our hypothesis that only one elongation system ..
- MECHANISM AND ROLE OF MICROSOMAL ETHANOL OXIDATIONCharles Lieber; Fiscal Year: 2001..In vivo, we will determine how changes in dietary lipids alter the activity of enzymes (including 2E1) in liver microsomes and how the latter correlates with changes in phospholipid composition...
- PRIMAQUINE-INDUCED HEMOLYTIC ANEMIADAVID MC MILLAN; Fiscal Year: 2004..each type of primaquine metabolite; 2) to elucidate the oxidative metabolism of primaquine in rat and human liver microsomes and hepatocytes, and identify GYP isoforms responsible for primaquine metabolism; and 3) to identify ..
- MECHANISMS OF TUMOR INITIATION BY BP AND DERIVATIVESErcole Cavalieri; Fiscal Year: 1993..are involved in the formation of 3- and 9-hydroxyBP, we will study the metabolism of 3- and 9-FBP with rat liver microsomes and analyze the formation of the respective hydroxy derivatives by high pressure liquid chromatography...
- BIOCHEMICAL TOXICOLOGY OF CYTOCHROME P-450Andrew Parkinson; Fiscal Year: 1990..related to these five rat liver microsomal isozymes) in extrahepatic microsomes from rats and in liver microsomes from other laboratory animals by immunochemical analysis and by analysis of testosterone metabolism...
- BIOCHEMICAL TOXICOLOGY OF CARBOXYESTERASESAndrew Parkinson; Fiscal Year: 1992..studies is to determine the molecular basis for the existence of multiple forms of carboxyesterases in rat liver microsomes, and to determine the function and regulation of these hydrolytic enzymes...
- VITAMIN K-DEPENDENT PROTEINS IN LIVER & ISOLATED CELLSReidar Wallin; Fiscal Year: 1992..Finally, purification of the physiologically important vitamin K1 reducing dehydrogenase enzyme in liver microsomes that mediates the antidotic effect of vitamin K1 will be attempted after proteolytic cleavage of the ..
- ROLE OF METABOLISM IN THE BILIARY EXCRETION OF DRUGWALTER LEVINE; Fiscal Year: 1990..Rat liver microsomes metabolize butter yellow (dimethylaminoazobenzene, DAB) by oxidative and reductive pathways...
- SHORT-CHAIN ACYLCARNITINES--FUNCTION AND ENZYMOLOGYLORAN BIEBER; Fiscal Year: 1993..Rev, BCH 57, 261 (1988(]; however, the roles for CAT and COT of liver microsomes are unknown due, in part, to the limited studies with these two enzymes...
- MECHANISM OF CARCINOGENESIS OF DIBENZ ACRIDINESubodh Kumar; Fiscal Year: 1991..pure DB(a,h)ACR-10,11-diols to DB(a,h)ACR-10,11-diols and DB(a,h)ACR-10,11-diol-8,9-epoxides, respectively by liver microsomes from control, 3-MC-treated and PB- treated rats, and by a purified and reconstituted cytochrome P-450c system,..
- Cytochrome P450 in Reperfusion InjuryRoberta Gottlieb; Fiscal Year: 2007..with CARD domain) and Bcl-xL inhibit CYP activity, while pro-apoptotic tBid stimulates CYP activity in rat liver microsomes. This proposal identifies cytochrome P450 monooxygenases as a previously underestimated factor in myocardial ..
- BIOTOXICITY OF ACTIVATED OLEFINSMasato Koreeda; Fiscal Year: 1980..Elucidation of the structure of the binding product using radioactive olefins in the presence of rat liver microsomes will be attempted...
- METABOLISM OF 5-METHYLCHRYSENE BY FISHNancy Shappell; Fiscal Year: 1993..parent hydrocarbon; and (3) to compare the data on the regio- and stereoselective metabolism of 5-MeC by fish liver microsomes with the data published for rat liver microsomes...
- INDUCTION AND MODE OF ACTION OF HEPATIC DRUG OXIDASEJohn Schenkman; Fiscal Year: 1992..a continuation of our efforts to isolate, purify, and characterize the remaining forms of cytochrome P-450 of liver microsomes of the untreated rat. We have, to date, isolated eight forms...
- VITAMIN E TURNOVER AND CHEMICAL TOXICITYDANIEL LIEBLER; Fiscal Year: 1992..liposomes) and to test the utility of these procedures in a more complex biological membrane system (rat liver microsomes)...
- ALCOHOL METABOLISM--ROLE OF P450 OXYGENASESMinor Coon; Fiscal Year: 2000..in animals by the diabetic state and by alcohol administration give additive effects on the P450 2E level in liver microsomes. If so, the oxidative damage and chemical pathology (including nitrosamine activation and acetaminophen ..
- CIGARETTE SMOKING OR PCBS EFFECTS ON ESTRADIOLBao Ting Zhu; Fiscal Year: 1999..3).Determine the profile of NADPH-dependent estradiol metabolites formed by liver microsomes from cigarette smokers and matched nonsmokers. (4)...
- INHIBITION OF BREAST CARCINOGENESIS BY DIBENZOYLMETHANEMou Tuan Huang; Fiscal Year: 1999..the effects of dietary DBM on the formation of mammary gland DNA-[3H]DMBA adducts and DMBA metabolism by liver microsomes. Our proposed studies will provide information on the potency of dietary DBM and on the mechanisms of its ..
- ROLE OF CYTOCHROMES P450 IN ISOFLAVONE METABOLISMElizabeth Roberts; Fiscal Year: 2001..goal of this research is to investigate the metabolism of isoflavones by cytochromes P450 using rat and human liver microsomes, heterologously-expressed human cytochromes P450, primary cultured rat hepatocytes, and breast MCF-7, MCF-10A,..
- TUMOR NECROSIS FACTOR: PURIFICATION AND MODE OF ACTIONSaul Green; Fiscal Year: 1980..TNF-like activity has been extracted from liver microsomes of normal mice and from CP-endotoxin treated mice...
- PORPHYRIN BIOSYNTHESIS IN NORMAL AND DISEASE STATESJAMES KUSHNER; Fiscal Year: 2001..We will also measure oxidation of substrates of URO-D and uroporphyrinogen III cosynthase by liver microsomes from rats given P450 inducers to determine if substrate oxidation is responsible for the preponderance of ..
- SELECTIVE DEPLETION OF ALKYLTRANSFERASE IN TUMOR CELLSM Dolan; Fiscal Year: 1999..The metabolic pathway of selected analogs will be determined in vitro using rat and human liver microsomes and cytosol...
- METABOLISM OF ACETYLAMINOFLOURENE BY RAINBOW TROUTHARISH SIKKA; Fiscal Year: 1993..research are: (1) to investigate the in vitro metabolism of AAF and N-hydroxy-AAF by Shasta rainbow trout liver microsomes with regard to the rates of metabolism and metabolite profile, (2) to examine the metabolism of AAF in ..
- ANTINEOPLASTIC DRUG HEPATIC INTERACTIONSDean Brenner; Fiscal Year: 1990..Dox and doxorubicinol rates of metabolism in healthy and perturbed liver microsomes will be measured...
- EFFECTS OF ETHANOL AND ANESTHETICS ON BIOLOGIC MEMBRANESTHEODORE TARASCHI; Fiscal Year: 1993..tolerance, or the inability of the membrane to be disordered by ethanol or anesthetics, has been shown in liver microsomes and mitochondria to be caused by alterations in particular anionic phospholipids...
- BIOCHEMICAL INTERACTIONS IN CHLOROPROPANE TOXICITYROBERT VOLP; Fiscal Year: 1990..The second objective will be pursued using liver microsomes incubated with radiolabelled CP...
- DISRUPTION OF ESTROGENIC RESPONSES BY PCB-PAH MIXTURESKathleen Arcaro; Fiscal Year: 2002..extent to which the estrogenic and anti-estrogenic activity of a mixture is altered by metabolism in human liver microsomes, and identify the major active metabolites...
- DNA DAMAGE AND MUTAGENICITY OF OCHRATOXIN ARichard Manderville; Fiscal Year: 2002..Utilizing an Fe-porphyrin/hydrogen peroxide oxidation system, copper(II) and liver microsomes to model the metabolic activation of OTA, the ability of OTA/OTQ to mediate DNA alkylation will be ..
- Human CYP2B6: Induction by ethanol and polymorphismsLeah Hesse; Fiscal Year: 2007..Depending on exposure duration, alcohol induces or inhibits drug metabolism. Human liver microsomes from donors reported to have consumed at least 14 alcoholic beverages per week have high CYP2B6 activity (..
- Isozyme Identification of Metabolic Pathways of HerbalsP Gunaratna; Fiscal Year: 2001..Metabolism of these compounds will be investigated in vitro in liver microsomes and expressed human enzymes...
- NATURAL PRODUCT DERIVATIVES THAT POTENTLY INHIBIT HIV-1Graham Allaway; Fiscal Year: 2002..5 hours following IV administration to rats, and metabolism studies in human and rat liver microsomes indicate it may have a longer half-life and greater oral bioavailability in humans...
- N-GLUCOSYLATION OF BARBITURATES AND RELATED DRUGSWILLIAM SOINE; Fiscal Year: 1993..A sensitive radiochemical assay will be used to measure phenobarbital N-glucosylation in vitro using mouse liver microsomes and to characterize this N-glucosyltransferase enzyme...
- UDP-GLUCURONYL-TRANSFERASE AND RADIOCONTRAST MEDIAADRIANA COBO FRENKEL; Fiscal Year: 1980..Among the enzymes to be investigated are UDP-Glucuronyl Transferase (UDPGT) and the cytochrome P450 of liver microsomes. The possible metabolities of RCM formed by the action of the drug metabolizing enzymes will be isolated and ..
- DETERMINANTS OF CARCINOGEN ACTIVATION/DETOXIFICATIONEric Johnson; Fiscal Year: 1980..Multiple forms of the cytochrome have been isolated in our laboratory from rabbit liver microsomes. These forms can be distinguished by polyacrylamide gel electrophoresis in the presence of sodium dodecyl ..
- RETINOID UDP-GLUCURONOSYLTRANSFERASESAnna Radominska Pandya; Fiscal Year: 2000..the following specific aims are proposed: 1) characterize retinoid glucuronidating activity in rat liver microsomes; 2) identify and isolate retinoid UGT protein(s) from rat liver microsomal fractions; and 3) identify ..
- EFFECT OF GINSENOSIDES ON CYTOCHROME P450Thomas Chang; Fiscal Year: 2001..These studies will be performed in vitro by employing recombinant cytochrome P450 enzymes, human liver microsomes, and cell culture models (i.e., MCF-7 human breast carcinoma cells) of cytochrome P450.
- Acetaminophen PharmacogeneticsMichael H Court; Fiscal Year: 2010....
- Mechanisms of adverse host responses to antibioticsMichael Court; Fiscal Year: 2006..unreadable] [unreadable] [unreadable]..
- MECHANISM OF INDUCTION OF OLFACTORY TUMORS BY ALACHLORMary Beth Genter; Fiscal Year: 2002....
- RECEPTOR MEDIATED OXIDATIVE STRESSHOWARD SHERTZER; Fiscal Year: 2003..These studies will improve our understanding of how PHAHs such as TCDD generate oxidative stress and mutagenesis, leading to better models for risk assessment and novel strategies for intervention in PHAH-mediated toxicity. ..
- REGULATION OF CYTOCHROME P4503A ACTIVITY IN THE ELDERLYLisa von Moltke; Fiscal Year: 2004....
- Extracellular matrix in chloracetanilide carcinogenesisMary Beth Genter; Fiscal Year: 2004..abstract_text> ..
- Sphingolipid signaling in olfactory mucosaMary Beth Genter; Fiscal Year: 2004..abstract_text> ..
- Glutathione in Environmental Toxicity and DiseaseHOWARD SHERTZER; Fiscal Year: 2007..Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease. ..
- ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSEDavid Greenblatt; Fiscal Year: 2002..The in vitro model, if validated, has the potential to provide clinically important information on interactions involving HIV treatments and abusable drugs, at relatively low cost and with no human drug exposure. ..
- CHRONIC BENZODIAZEPINES: BEHAVIOR AND NEUROCHEMISTRYDavid Greenblatt; Fiscal Year: 2005....