Research Topics
Genomes and GenesSpecies | Zeruesenay DestaSummaryAffiliation: Indiana University Country: USA Publications
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Publications
Efavirenz primary and secondary metabolism in vitro and in vivo: identification of novel metabolic pathways and cytochrome P450 2A6 as the principal catalyst of efavirenz 7-hydroxylationEvan T Ogburn
Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Drug Metab Dispos 38:1218-29. 2010..Efavirenz may be a valuable dual phenotyping tool to study CYP2B6 and CYP2A6, and this should be further tested in vivo...
The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6Zeruesenay Desta
Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
Drug Metab Dispos 30:336-43. 2002..Metoclopramide elimination is likely to be slowed in poor metabolizers of CYP2D6 or in patients taking inhibitors of this isoform, whereas metoclopramide itself could reduce the clearance of CYP2D6 substrate drugs...- 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. 2004..Variable activity of these P450s, brought about by genetic polymorphisms and drug interactions, may alter the balance of TAM effects in vivo... - Rapid identification of the hepatic cytochrome P450 2C19 activity using a novel and noninvasive [13C]pantoprazole breath testZeruesenay Desta
Indiana University School of Medicine, Indianapolis, IN 46202, USA
J Pharmacol Exp Ther 329:297-305. 2009..74; p = 0.038). These feasibility data suggest that the [(13)C]pantoprazole breath test is a reliable, rapid, and noninvasive probe of CYP2C19 and seems to be a useful tool to optimize drug therapy metabolized by CYP2C19... 
Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and ageZ Desta
Department of Medicine, Indiana University, Indianapolis, Indiana, USA
Clin Pharmacol Ther 90:693-700. 2011..CYP2A6 metabolic status, along with BMI and age, may serve as a biomarker of the efficacy of letrozole treatment or a predictor of adverse effects...- In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycinZeruesenay Desta
Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
J Clin Psychopharmacol 22:162-8. 2002..In addition, the possibility that these drugs could alter pimozide disposition through effects on transport proteins or via promoter repression cannot be ruled out... - Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitroZeruesenay Desta
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
Pharmacogenomics 8:547-58. 2007..To determine the influence of cytochrome P450 2B6 (CYP2B6) genotype on the rate of oxidative efavirenz metabolism in human liver microsomes... - Effects of the CYP2B6*6 allele on catalytic properties and inhibition of CYP2B6 in vitro: implication for the mechanism of reduced efavirenz metabolism and other CYP2B6 substrates in vivoCong Xu
Indiana University School of Medicine, Indianapolis, IN 46202, USA
Drug Metab Dispos 40:717-25. 2012..1 μM). In conclusion, our data suggest the CYP2B6*6 allele influences metabolic activity by altering substrate binding and catalytic activity in a substrate- and Cyt b5-dependent manner. It may also confer susceptibility to inhibition... - Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3ASeongwook Jeong
Division of Clinical Pharmacology, Department of Medicine, Indiana University, Indianapolis, USA
Antimicrob Agents Chemother 53:541-51. 2009..Clinicians should be aware of these interactions and monitor patients for adverse effects or failure of therapy... - A mixture model approach in gene-gene and gene-environmental interactions for binary phenotypesLang Li
Division of Biostatistics, Department of Medicine, Indiana University, Indianapolis, Indiana46202, USA
J Biopharm Stat 18:1150-77. 2008..The mixture model approach has the highest recovery probability to recover the true partition in the simulation studies. Its applications are exemplified in interim data analyses for two cancer studies... - CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatmentYan Jin
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
J Natl Cancer Inst 97:30-9. 2005.... - Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatmentSilvana Borges
Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, 46202, USA
Clin Pharmacol Ther 80:61-74. 2006..We conducted a prospective trial in 158 patients with breast cancer who were taking tamoxifen to further understand the effect of CYP2D6 genotype and concomitant medications on endoxifen plasma concentrations... - Estimating a positive false discovery rate for variable selection in pharmacogenetic studiesLang Li
Department of Medicine, Division of Biostatistics, Indiana University, Indianapolis, Indiana 46202, USA
J Biopharm Stat 17:883-902. 2007..Data analysis is illustrated with a pharmacogenetics example... - Composite functional genetic and comedication CYP2D6 activity score in predicting tamoxifen drug exposure among breast cancer patientsSilvana Borges
Division of Biostatistics Clinical Pharmacology, Indiana University, School of Medicine, 410 W 10th St, HITS 3000, Indianapolis, IN 46202 e mail
J Clin Pharmacol 50:450-8. 2010..However, endoxifen phenotypes still varied substantially, even with incorporation of CYD2D6 genotype and inhibiting factors, suggesting that other, as yet unidentified factors must be involved in tamoxifen activation... - Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetineVered Stearns
The Breast Cancer Program, Department of Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA
J Natl Cancer Inst 95:1758-64. 2003..Coadministration of paroxetine decreased the plasma concentration of endoxifen. Our data suggest that CYP2D6 genotype and drug interactions should be considered in women treated with tamoxifen... - Endoxifen, a secondary metabolite of tamoxifen, and 4-OH-tamoxifen induce similar changes in global gene expression patterns in MCF-7 breast cancer cellsYoung Chai Lim
Division of Clinical Pharmacology, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, IN 46202, USA
J Pharmacol Exp Ther 318:503-12. 2006..We conclude that endoxifen and 4-OH-Tam have similar effects on global gene expression patterns in MCF-7 cells and that the majority of the affected genes are estrogen-regulated genes... - The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activityBryan A Ward
Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
J Pharmacol Exp Ther 306:287-300. 2003..Efavirenz may be a valuable phenotyping tool to study the role of CYP2B6 in human drug metabolism... - Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitroSeongwook Jeong
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Cancer Chemother Pharmacol 64:867-75. 2009..To determine the inhibitory potency of letrozole and its main human metabolite, 4,4'-methanol-bisbenzonitrile, on the activities of eight cytochrome P450 (CYP) enzymes... - QT analysis: a complex answer to a 'simple' problemLang Li
Division of Biostatistics, Department of Medicine, Indiana University 46202 2678, USA
Stat Med 23:2625-43. 2004..1-0.2 ms). The two-step off-drug QT correction analysis is shown to be almost as efficient as our one-step off- and on-drug QT analysis... - Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: implications for cyclophosphamide metabolismJames M Rae
Division of Clinical Pharmacology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA
Drug Metab Dispos 30:525-30. 2002..Furthermore, thioTEPA may prove to be a valuable new tool for the study of this important drug-metabolizing enzyme... - Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitroBryan A Ward
Indiana University School of Medicine, Department of Medicine Division of Clinical Pharmacology, 1001 West 10th Street, OPD W 320, Indianapolis, Indiana, USA
Br J Clin Pharmacol 58:277-87. 2004..To confirm the identity of the major metabolites of domperidone and to characterize the cytochrome P450s (CYPs) involved in their formation... - Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancerWenjie Jessie Lu
Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Indiana University Simon Cancer Center, Indiana University School of Medicine, 1001 West 10th Street, Room 7123, Myers Building, Indianapolis, IN 46202, USA
Breast Cancer Res Treat 131:473-81. 2012..Relationships between tamoxifen metabolite concentrations and clinical outcomes may be complex, and the biologic mechanisms that underlie these relationships may include aromatase inhibition... - A penalized mixture model approach in genotype/phenotype association analysis for quantitative phenotypesLang Li
Division of Biostatistics, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN
Cancer Inform 9:93-103. 2010..The power and recovery rate of the true partition for the mixture model approach are investigated in statistical simulation studies, where it outperforms another published method... - Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozoleLauren Nicole Bell
Division of Clinical Pharmacology, Wishard Memorial Hospital, WD Myers Bldg, W7123, 1001 West 10th St, Indianapolis, IN 46202, USA
J Clin Pharmacol 52:1852-60. 2012..In conclusion, AI treatment and/or washout of tamoxifen induced detrimental changes in the lipid profile of postmenopausal women with breast cancer... - Abacavir, didanosine and tenofovir do not induce inflammatory, apoptotic or oxidative stress genes in coronary endothelial cellsChul Kim
Department of Cellular and Integrative Physiology, Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Antivir Ther 16:1335-9. 2011..We examined the impact of these drugs on the expression levels of the proinflammatory, oxidative stress and apoptosis regulating genes in HCAECs... - Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trialKyung-Hoon Lee
Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Memorial Hospital, 1001 West Tenth Street, Myers Building W7123, Indianapolis, IN 46202, USA
J Chromatogr B Analyt Technol Biomed Life Sci 791:245-53. 2003..B 655 (1994) 261]. The coefficients of variation for the midpoint of the standard curve for each compound were less than 10%. This method was applied to a pharmacokinetic study of tamoxifen disposition in breast cancer patients... - Methadone: a substrate and mechanism-based inhibitor of CYP19 (aromatase)Wenjie Jessie Lu
Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Drug Metab Dispos 38:1308-13. 2010..Methadone is metabolized by CYP19 and may act as a potent inhibitor of CYP19 in vivo. These findings may contribute to variability in methadone clearance, to drug-drug interactions, and to side effects observed in individual patients... - In vitro and in vivo oxidative metabolism and glucuronidation of anastrozoleLandry K Kamdem
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA
Br J Clin Pharmacol 70:854-69. 2010..Little information is available regarding the metabolic routes of anastrozole and the specific enzymes involved. We characterized anastrozole oxidative and conjugation metabolism in vitro and in vivo... - Clinical significance of the cytochrome P450 2C19 genetic polymorphismZeruesenay Desta
Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Hospital, Indianapolis 46202, USA
Clin Pharmacokinet 41:913-58. 2002..Finally, many studies have attempted to identify relationships between CYP2C19 genotype and phenotype and susceptibility to xenobiotic-induced disease, but none of these are compelling... - Tamoxifen and its metabolites cause acute vasorelaxation of aortic rings by inducing vasodilator prostanoid synthesisMarcelo F Montenegro
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil
J Cardiovasc Pharmacol 58:647-53. 2011..These results show that Tam and its metabolites cause acute vasorelaxation by inducing vasodilator prostanoids synthesis... - Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel responseRolf P Kreutz
Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN, USA
Clin Pharmacol 4:13-20. 2012.... - Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifenYoung Chai Lim
Division of Clinical Pharmacology, Indiana University School of Medicine, 1001 West 10th Street, WD Myers Bldg, W7123, Indianapolis, Indiana 46202, USA
Cancer Chemother Pharmacol 55:471-8. 2005.... - Sequence diversity and functional characterization of the 5'-regulatory region of human CYP2C19Million Arefayene
Department of Medicine Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Pharmacogenetics 13:199-206. 2003..These data make possible future studies to elucidate the molecular mechanisms by which CYP2C19 can be induced in clinical settings and the consequences of genetic variability in its promoter... - Identification of genetic variants in the human indoleamine 2,3-dioxygenase (IDO1) gene, which have altered enzyme activityMillion Arefayene
Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA
Pharmacogenet Genomics 19:464-76. 2009..We identified genetic variations in the IDO1 gene and evaluated their functional activities using in-vitro transfection studies... - Contribution of N-glucuronidation to efavirenz elimination in vivo in the basal and rifampin-induced metabolism of efavirenzDoo Yeoun Cho
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Antimicrob Agents Chemother 55:1504-9. 2011.... - In vitro cytochrome P450-mediated metabolism of exemestaneLandry K Kamdem
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
Drug Metab Dispos 39:98-105. 2011..None of them markedly inhibited the formation of MI. In summary, exemestane seems to be metabolized to MI by multiple P450s that include CYP4A11 and CYP1A1/2, whereas its oxidation to MII is primarily mediated by CYP3A... - Stereoselective and regiospecific hydroxylation of ketamine and norketamineZeruesenay Desta
Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA
Xenobiotica 42:1076-87. 2012..Large variations in HNK concentrations were observed suggesting that pharmacogenetics and/or metabolic drug interactions may play a role in therapeutic response... - Anti-inflammatory treatment with pentoxifylline improves HIV-related endothelial dysfunction: a pilot studySamir K Gupta
Department of Medicine, Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, USA
AIDS 24:1377-80. 2010..Pentoxifylline may reverse HIV-related endothelial dysfunction by directly inhibiting the endothelial leukocyte adhesion pathway... - Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes studyRolf P Kreutz
Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana
Pharmacotherapy 30:787-96. 2010..To investigate the potential impact of proton pump inhibitors (PPIs) on the effectiveness of clopidogrel in preventing recurrent ischemic events after percutaneous coronary intervention (PCI) with stent placement... - Effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites: exploration of a novel CYP2B6 phenotyping indexFen Jiang
Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, South Korea Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, South Korea Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA
Br J Clin Pharmacol 75:244-53. 2013..The 8,14-dihydroxyefaviremz : efavirenz AUC(0,120 h) ratio is attractive as a candidate phenotyping index for CYP2B6 activity in vivo... - Variability of heart rate correction methods for the QT intervalMehul Desai
Division of Clinical Pharmacology, Department of Medicine, Indiana University, Indianapolis, IN, USA, and Department of Cardiological Sciences, St George's Hospital Medical School, London, UK
Br J Clin Pharmacol 55:511-7. 2003..The interindividual QTc changes from baseline varied significantly depending on the method of correction used... - Germline pharmacogenetics of tamoxifen response: have we learned enough?Zeruesenay Desta
J Clin Oncol 25:5147-9. 2007 - Cytochrome P450 2D6 and homeobox 13/interleukin-17B receptor: combining inherited and tumor gene markers for prediction of tamoxifen resistanceMatthew P Goetz
Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Clin Cancer Res 14:5864-8. 2008..We sought to determine the combined effect of inherited (CYP2D6) and somatic (HOXB13/IL17BR) gene variation in tamoxifen-treated breast cancer... - Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritisKazuki Takada
National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA
Arthritis Rheum 50:2202-10. 2004..We conducted a retrospective cohort study to test whether genetic polymorphisms of these enzymes are associated with the toxicity of, and clinical response to, cyclophosphamide in patients with lupus nephritis... - The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifenMatthew P Goetz
Department of Oncology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN, 55905, USA
Breast Cancer Res Treat 101:113-21. 2007.... - Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashesMatthew P Goetz
Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
J Clin Oncol 23:9312-8. 2005..Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown...
Research Grants
- CYP2B6 genetic variations and drug interactionsZeruesenay Desta; Fiscal Year: 2007..Together, these studies will lay the groundwork for improved therapy with a growing list of drugs that are metabolized by CYP2B6 through optimizing beneficial effects and avoiding adverse drug reactions. ..
- CYP2B6 genetic variations and drug interactionsZeruesenay Desta; Fiscal Year: 2009..Together, these studies will lay the groundwork for improved therapy with a growing list of drugs that are metabolized by CYP2B6 through optimizing beneficial effects and avoiding adverse drug reactions. ..
- CYP2B6 genetic variations and drug interactionsZeruesenay Desta; Fiscal Year: 2010..Together, these studies will lay the groundwork for improved therapy with a growing list of drugs that are metabolized by CYP2B6 through optimizing beneficial effects and avoiding adverse drug reactions. ..
- CYP2B6 genetic variations and drug interactionsZeruesenay Desta; Fiscal Year: 2010..Together, these studies will lay the groundwork for improved therapy with a growing list of drugs that are metabolized by CYP2B6 through optimizing beneficial effects and avoiding adverse drug reactions. ..