Jiunn H Lin

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi request reprint Pharmacokinetic and pharmacodynamic variability: a daunting challenge in drug therapy
    Jiunn H Lin
    Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Curr Drug Metab 8:109-36. 2007
  2. ncbi request reprint In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4
    Y Sahali-Sahly
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Chem Res Toxicol 9:1007-12. 1996
  3. ncbi request reprint Applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics
    J H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Drug Metab Dispos 26:1202-12. 1998
  4. ncbi request reprint Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library
    T A Rano
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 10:1527-30. 2000
  5. ncbi request reprint In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results
    M Yamazaki
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Pharmacol Exp Ther 296:723-35. 2001
  6. ncbi request reprint Clinical relevance of P-glycoprotein in drug therapy
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Drug Metab Rev 35:417-54. 2003
  7. ncbi request reprint Applications and limitations of genetically modified mouse models in drug discovery and development
    Jiunn H Lin
    Department of Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, West Point, Pennsylvania, USA
    Curr Drug Metab 9:419-38. 2008
  8. ncbi request reprint Role of P-glycoprotein in pharmacokinetics: clinical implications
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Clin Pharmacokinet 42:59-98. 2003
  9. ncbi request reprint Sense and nonsense in the prediction of drug-drug interactions
    J H Lin
    Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Drug Metab 1:305-31. 2000
  10. ncbi request reprint Complexities of glucuronidation affecting in vitro in vivo extrapolation
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Curr Drug Metab 3:623-46. 2002

Collaborators

Detail Information

Publications75

  1. ncbi request reprint Pharmacokinetic and pharmacodynamic variability: a daunting challenge in drug therapy
    Jiunn H Lin
    Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Curr Drug Metab 8:109-36. 2007
    ..Finally, the application and limitation of the concept of personalized medicine will be briefly discussed...
  2. ncbi request reprint In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4
    Y Sahali-Sahly
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Chem Res Toxicol 9:1007-12. 1996
    ..One or more of these electrophilic species may be responsible for the autocatalytic destruction of cytochrome P450 enzymes which accompanies L-754,394 metabolism in vitro and in vivo...
  3. ncbi request reprint Applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics
    J H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Drug Metab Dispos 26:1202-12. 1998
    ..This review examines the applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics...
  4. ncbi request reprint Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library
    T A Rano
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 10:1527-30. 2000
    ..Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates...
  5. ncbi request reprint In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results
    M Yamazaki
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Pharmacol Exp Ther 296:723-35. 2001
    ..v. administration. These results provide a rationale for predicting in vivo relevance of P-gp in human from in vitro data using human P-gp-expressing cells...
  6. ncbi request reprint Clinical relevance of P-glycoprotein in drug therapy
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Drug Metab Rev 35:417-54. 2003
    ..From animal and clinical studies, it is evident that P-gp plays a very important role in CNS penetration of drugs, whereas the effect of P-gp on drug absorption is not as important as generally believed...
  7. ncbi request reprint Applications and limitations of genetically modified mouse models in drug discovery and development
    Jiunn H Lin
    Department of Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, West Point, Pennsylvania, USA
    Curr Drug Metab 9:419-38. 2008
    ..Accordingly, it is important to keep in mind that an animal engineered to express a human gene and its protein is still an animal...
  8. ncbi request reprint Role of P-glycoprotein in pharmacokinetics: clinical implications
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Clin Pharmacokinet 42:59-98. 2003
    ..Unless the relative contribution of P-glycoprotein and CYP3A4 to drug interactions can be quantitatively estimated, care should be taken when exploring the underlying mechanism of such interactions...
  9. ncbi request reprint Sense and nonsense in the prediction of drug-drug interactions
    J H Lin
    Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Drug Metab 1:305-31. 2000
    ..Theoretic considerations are briefly reviewed, and representative examples are drawn from literature to illustrate the sense and nonsense in predicting in vivo drug interactions...
  10. ncbi request reprint Complexities of glucuronidation affecting in vitro in vivo extrapolation
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Curr Drug Metab 3:623-46. 2002
    ..In contrast to CYP-mediated interactions, with a few exceptions, the magnitude of UGT-mediated interactions are less than 2-fold because of the relatively high UGT Km values and substrate overlap among the multiple isozymes...
  11. ncbi request reprint Tissue distribution and pharmacodynamics: a complicated relationship
    Jiunn H Lin
    Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Curr Drug Metab 7:39-65. 2006
    ..Also, validity of some key assumptions that are used to relate the processes of tissue distribution with pharmacologic activity will be discussed...
  12. ncbi request reprint Route-dependent nonlinear pharmacokinetics of a novel HIV protease inhibitor: involvement of enzyme inactivation
    J H Lin
    Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Drug Metab Dispos 28:460-6. 2000
    ..Data from in vitro and in vivo studies suggested that the dose- and route-dependent pharmacokinetics were due mainly to the inactivation (destruction) of the enzymes responsible for its own metabolism...
  13. ncbi request reprint CYP induction-mediated drug interactions: in vitro assessment and clinical implications
    Jiunn H Lin
    Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Pharm Res 23:1089-116. 2006
    ..Finally, assessment of the potential of CYP induction at the drug discovery and development stage will be discussed...
  14. ncbi request reprint How significant is the role of P-glycoprotein in drug absorption and brain uptake?
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Drugs Today (Barc) 40:5-22. 2004
    ..This review provides an overview of the role of P-gp in drug absorption and brain uptake, and explores possible factors that may explain the quantitative differences in the impact of P-gp on drug absorption and brain uptake...
  15. ncbi request reprint Drug-drug interaction mediated by inhibition and induction of P-glycoprotein
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, WP75A 203, West Point, PA 19486, USA
    Adv Drug Deliv Rev 55:53-81. 2003
    ..Therefore, care should be exercised when interpreting drug interaction data and exploring the underlying mechanisms of drug interactions...
  16. ncbi request reprint CSF as a surrogate for assessing CNS exposure: an industrial perspective
    Jiunn H Lin
    Department of Preclinical Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Curr Drug Metab 9:46-59. 2008
    ..Depending on the physicochemical properties of drugs and the site/timing of CSF sampling, the unbound drug concentration at the biophase within the brain could differ significantly from the corresponding CSF drug concentration...
  17. ncbi request reprint Inhibition and induction of cytochrome P450 and the clinical implications
    J H Lin
    Merck Research Laboratories, West Point, Pennsylvania, USA
    Clin Pharmacokinet 35:361-90. 1998
    ..Thus, careful evaluation of potential drug interactions of a new drug candidate during the early stage of drug development is essential...
  18. ncbi request reprint Transporter-mediated drug interactions: clinical implications and in vitro assessment
    Jiunn H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Expert Opin Drug Metab Toxicol 3:81-92. 2007
    ..The potential risk of transporter-mediated drug interactions might be underestimated if only plasma concentrations are monitored...
  19. ncbi request reprint Novel HIV-1 protease inhibitors active against multiple PI-resistant viral strains: coadministration with indinavir
    Nancy J Kevin
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:4027-30. 2003
    ..The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment...
  20. ncbi request reprint HIV protease inhibitors with picomolar potency against PI-Resistant HIV-1 by extension of the P3 substituent
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:2569-72. 2003
    ..Inhibition of multiple P450 isoforms is dependent on the regiochemistry of the pyridyl nitrogen in these compounds...
  21. ncbi request reprint The design, synthesis and evaluation of novel HIV-1 protease inhibitors with high potency against PI-resistant viral strains
    Fengqi Zhang
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:2573-6. 2003
    ..Compound 10 also demonstrated favorable in vivo pharmacokinetics in animal models...
  22. ncbi request reprint In vitro and in vivo CYP3A64 induction and inhibition studies in rhesus monkeys: a preclinical approach for CYP3A-mediated drug interaction studies
    Thomayant Prueksaritanont
    Department of Drug Metabolism, WP75 100, Merck Research Laboratories, West Point, PA 19486, USA
    Drug Metab Dispos 34:1546-55. 2006
    ..These findings suggest the potential applicability of the in vitro-in vivo relationship approach in rhesus monkeys for studying CYP3A-mediated interactions in humans...
  23. ncbi request reprint Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains
    Yuan Cheng
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 12:2419-22. 2002
    ..The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains...
  24. ncbi request reprint Orally bioavailable highly potent HIV protease inhibitors against PI-resistant virus
    Zhijian Lu
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 15:5311-4. 2005
    ..Chemistry and biology are described...
  25. ncbi request reprint Mechanistic studies on metabolic interactions between gemfibrozil and statins
    Thomayant Prueksaritanont
    Department of Drug Metabolism, WP75 100, Merck Research Laboratories, West Point, PA 19486, USA
    J Pharmacol Exp Ther 301:1042-51. 2002
    ..Collectively, the results of these studies provide metabolic insight into the nature of drug-drug interaction between GFZ and statins, and a possible explanation for the enhanced susceptibility of CVA to interactions with GFZ...
  26. ncbi request reprint HIV-1 protease inhibitors with picomolar potency against PI-resistant HIV-1 by modification of the P1' substituent
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:3323-6. 2003
    ..The poor to modest bioavailability of these compounds may correlate in part to their aqueous solubility...
  27. ncbi request reprint Effects of fibrates on metabolism of statins in human hepatocytes
    Thomayant Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Drug Metab Dispos 30:1280-7. 2002
    ....
  28. ncbi request reprint Synthesis and activity of novel HIV protease inhibitors with improved potency against multiple PI-resistant viral strains
    Joseph L Duffy
    Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 12:2423-6. 2002
    ..The trifluoroethyl substituent also affords a slower clearance rate in vivo (dogs); however, this may be due to more potent inhibition of at least two P450 isoforms...
  29. ncbi request reprint Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin
    Jerome H Hochman
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Pharm Res 21:1686-91. 2004
    ..In this study, P-glycoprotein (P-gp) mediated efflux of simvastatin (SV), simvastatin acid (SVA), and atorvastatin (AVA) and inhibition of P-gp by SV, SVA, and AVA were evaluated to assess the role of P-gp in drug interactions...
  30. ncbi request reprint Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug-drug interactions with P-glycoprotein
    Jerome H Hochman
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Drug Metab 3:257-73. 2002
    ..We will discuss the role of P-gp in drug disposition, the biochemistry of P-gp efflux as it relates to model systems to study drug interactions with P-gp, and the implementation of P-gp assay models within the drug discovery process...
  31. ncbi request reprint Interconversion pharmacokinetics of simvastatin and its hydroxy acid in dogs: effects of gemfibrozil
    Thomayant Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Pharm Res 22:1101-9. 2005
    ....
  32. ncbi request reprint Design and synthesis of highly potent HIV protease inhibitors with activity against resistant virus
    Zhijian Lu
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 13:1821-4. 2003
    ..These compounds are active against various clinical viral isolates as well as wild-type virus. The synthesis and biological activity of these HIV protease inhibitors are discussed...
  33. ncbi request reprint Metabolic activation of a pyrazinone-containing thrombin inhibitor. Evidence for novel biotransformation involving pyrazinone ring oxidation, rearrangement, and covalent binding to proteins
    Rominder Singh
    Department of Drug Metabolism, Merck Research Labs, West Point, Pennsylvania, USA
    Chem Res Toxicol 16:198-207. 2003
    ..Elucidation of the metabolic activation pathways of I provides structural guidance for the design of thrombin inhibitors with decreased potential for the generation of chemically reactive intermediates...
  34. ncbi request reprint Species-dependent enantioselective plasma protein binding of MK-571, a potent leukotriene D4 antagonist
    J H Lin
    Merck Sharp and Dohme Research Laboratories, West Point, PA 19486
    Drug Metab Dispos 18:484-7. 1990
    ....
  35. ncbi request reprint Pharmacokinetics and interactions of a novel antagonist of chemokine receptor 5 (CCR5) with ritonavir in rats and monkeys: role of CYP3A and P-glycoprotein
    Sanjeev Kumar
    Department of Drug Metabolism, Merck Research Laboratories, Rahway, New Jersey, USA
    J Pharmacol Exp Ther 304:1161-71. 2003
    ..In contrast to rats, the effects of P-gp in determining the intestinal absorption of MRK-1 appeared less significant in rhesus monkeys at either dose...
  36. ncbi request reprint Complicating factors in safety testing of drug metabolites: kinetic differences between generated and preformed metabolites
    Thomayant Prueksaritanont
    Department of Drug Metabolism, WP75 100, Merck Research Laboratories, West Point, PA 19486, USA
    Toxicol Appl Pharmacol 217:143-52. 2006
    ....
  37. ncbi request reprint A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells
    Mark W Embrey
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 15:4550-4. 2005
    ..Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC(95) of 40 nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs...
  38. ncbi request reprint P450 interaction with HIV protease inhibitors: relationship between metabolic stability, inhibitory potency, and P450 binding spectra
    M Chiba
    Department of Drug Metabolism, West Point, Pennsylvania, USA
    Drug Metab Dispos 29:1-3. 2001
    ....
  39. ncbi request reprint Metabolism-based drug-drug interactions: what determines individual variability in cytochrome P450 induction?
    Cuyue Tang
    Department of Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486 0004, USA
    Drug Metab Dispos 33:603-13. 2005
    ....
  40. pmc A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase
    Daria J Hazuda
    Department of Biological Chemistry, Merck Research Laboratories, P O Box 4, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 101:11233-8. 2004
    ..These studies provide a structural basis and rationale for developing integrase inhibitors with the potential for unique and nonoverlapping resistance profiles...
  41. ncbi request reprint Using real-time quantitative TaqMan RT-PCR to evaluate the role of dexamethasone in gene regulation of rat P-glycoproteins mdr1a/1b and cytochrome P450 3A1/2
    Qin Mei
    Department of Drug Metabolism, Merck Research Laboratories, WP75 200, West Point, PA 19486, USA
    J Pharm Sci 93:2488-96. 2004
    ..The disparity of the impact of Dex on the CYP 3A and Pgp expression in these studies suggest that the regulation of Pgp expression is very complex and is difficult to predict solely based on the PXR response to xenobiotics...
  42. ncbi request reprint P450 interaction with farnesyl-protein transferase inhibitors metabolic stability, inhibitory potency, and P450 binding spectra in human liver microsomes
    M Chiba
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Biochem Pharmacol 62:773-6. 2001
    ....
  43. ncbi request reprint Effect of dexamethasone on the intestinal first-pass metabolism of indinavir in rats: evidence of cytochrome P-450 3A [correction of P-450 A] and p-glycoprotein induction
    J H Lin
    Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Drug Metab Dispos 27:1187-93. 1999
    ....
  44. ncbi request reprint Effects of fibrates on human organic anion-transporting polypeptide 1B1-, multidrug resistance protein 2- and P-glycoprotein-mediated transport
    M Yamazaki
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19846, USA
    Xenobiotica 35:737-53. 2005
    ..Considering the plasma protein binding and IC50 values for OATP1B1, only gemfibrozil appeared to have a potential to cause drug-drug interactions by inhibiting OATP1B1 at clinically relevant concentrations...
  45. ncbi request reprint Renal elimination of a novel and potent alphavbeta3 integrin antagonist in animals
    T Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Xenobiotica 34:1059-74. 2004
    ....
  46. ncbi request reprint Comparative disposition of [14C]ertapenem, a novel carbapenem antibiotic, in rat, monkey and man
    B K Wong
    Department of Drug Metabolism, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA
    Xenobiotica 34:379-89. 2004
    ..The specific inhibitor of dehydropeptidase-I, cilastatin, inhibited the in vivo and in vitro metabolism of ertapenem in rats, which suggested strongly that the hydrolysis of ertapenem in lung and kidney was mediated by this enzyme...
  47. ncbi request reprint Stereoselective hepatic disposition of a diastereomeric pair of alphavbeta3 antagonists in rat
    T Prueksaritanont
    Department of Drug Metabolism, Merck Reseach Laboratories, West Point, PA 19486, USA
    Xenobiotica 33:1125-37. 2003
    ....
  48. ncbi request reprint Disposition of a novel and potent alpha(v)beta3 antagonist in animals, and extrapolation to man
    T Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Xenobiotica 34:103-15. 2004
    ..These predicted values provided a basis for compound selection for further development...
  49. ncbi request reprint Interaction with indinavir to enhance systemic exposure of an investigational HIV protease inhibitor in rats, dogs and monkeys
    L Jin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Xenobiotica 33:643-54. 2003
    ..5. Enhancement in compound A systemic exposure by indinavir in humans, as predicted based on the in vivo animal and in vitro human liver microsomal data, was confirmed in subsequent clinical studies...
  50. ncbi request reprint Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4
    J H Hochman
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    J Pharmacol Exp Ther 292:310-8. 2000
    ..In summary, the results support a role of Pgp in increasing intestinal presystemic metabolism and in removal of CYP3A4-generated metabolites from the intracellular compartment...
  51. ncbi request reprint Dose-dependent plasma clearance of MK-826, a carbapenem antibiotic, arising from concentration-dependent plasma protein binding in rats and monkeys
    B K Wong
    Drug Metabolism, WP75 100, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Pharm Sci 88:277-80. 1999
    ..Clearance values based on unbound concentrations appeared independent of dose from 10 to 180 mg/kg, which is consistent with saturation of protein binding as the primary cause of the nonlinear pharmacokinetic behavior...
  52. ncbi request reprint PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites
    B K Wong
    Drug Metabolism, Merck Research Laboratories, WP75A 203, West Point, PA 19486, USA
    Drug Metab Dispos 29:313-8. 2001
    ..In vitro studies provided further support for the PSA specificity of metabolism; LNCaP cells mediated rapid metabolism of the conjugate, while DuPRO-1 cells, which are deficient in PSA, were incapable of metabolism...
  53. ncbi request reprint Physiological disposition of aerosolized MK-679 in rats
    D J Tocco
    Merck Sharp and Dohme Research Laboratories, West Point, PA 19486
    Drug Metab Dispos 20:428-31. 1992
    ..The results of this study suggest that inhalation of MK-679 should be a considered route of administration for the treatment of asthma...
  54. ncbi request reprint Interaction of diclofenac and quinidine in monkeys: stimulation of diclofenac metabolism
    W Tang
    Department of Drug Metabolism, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Pharmacol Exp Ther 291:1068-74. 1999
    ..5-fold in the presence of quinidine. These data suggest that the catalytic capacity of monkey hepatic CYP3A toward diclofenac metabolism is enhanced by quinidine...
  55. ncbi request reprint Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors
    B D Dorsey
    Departments of Medicinal Chemistry, Antiviral Research, Drug Metabolism, and Molecular Systems, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Med Chem 43:3386-99. 2000
    ..MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials...
  56. ncbi request reprint Comparison of imidazole- and 2-methyl imidazole-containing farnesyl-protein transferase inhibitors: interaction with and metabolism by rat hepatic cytochrome P450s
    C Tang
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    Drug Metab Dispos 28:680-6. 2000
    ..The different kinetic parameters of I and II may also explain the observation that no significant difference in pharmacokinetic behavior was seen after an i.v. administration of I and II to the rat...
  57. ncbi request reprint Comparative in vitro metabolism of indinavir in primates--a unique stereoselective hydroxylation in monkey
    M Chiba
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Xenobiotica 30:117-29. 2000
    ..3. The present study has demonstrated that monkeys were unique in their abilities to form the stereoselective metabolite and were not appropriate surrogates for the qualitative prediction of indinavir metabolism in human...
  58. ncbi request reprint P-glycoprotein-mediated efflux of indinavir metabolites in Caco-2 cells expressing cytochrome P450 3A4
    J H Hochman
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania, USA
    J Pharmacol Exp Ther 298:323-30. 2001
    ..These results are consistent with a role of Pgp in elimination of CYP3A4-generated metabolites and indicate that even relatively polar metabolites may be secreted from the cell by Pgp...
  59. ncbi request reprint Enzyme kinetics of cytochrome P450-mediated reactions
    M Shou
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Drug Metab 2:17-36. 2001
    ..Applications of these kinetic models can provide some new insights into the mechanism of P450-mediated drug-drug interactions...
  60. ncbi request reprint In vitro metabolism of indinavir in the human fetal liver microsomes
    M Chiba
    Department of Drug Metabolism I, Merck Research Laboratories, West Point, PA 19486, USA
    Drug Metab Dispos 25:1219-22. 1997
    ..The reason for the observed marked differences in the development-associated alteration may lie in the differences of substrate specificities between CYP3A isoforms...
  61. ncbi request reprint Metabolite-P450 complex formation by methylenedioxyphenyl HIV protease inhibitors in rat and human liver microsomes
    M Chiba
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Biochem Pharmacol 56:223-30. 1998
    ....
  62. ncbi request reprint Pharmacokinetics and metabolism of a RAS farnesyl transferase inhibitor in rats and dogs: in vitro-in vivo correlation
    R Singh
    Department of Drug Metabolism, Merck Research Labs, West Point, Pennsylvania 19486, USA
    Drug Metab Dispos 29:1578-87. 2001
    ..Animal and human liver microsomal intrinsic clearance values were scaled to predict hepatic clearance and half-life in humans, and the predicted values were in good agreement to the in vivo data...
  63. ncbi request reprint Differences in the absorption, metabolism and biliary excretion of a diastereomeric pair of alphavbeta3-antagonists in rat: limited role of P-glycoprotein
    T Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA
    Xenobiotica 32:207-20. 2002
    ....
  64. ncbi request reprint beta-Oxidation of simvastatin in mouse liver preparations
    T Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Drug Metab Dispos 29:1251-5. 2001
    ..Additionally, the present finding of CoASH-dependent formation of SV substantiates a mechanism proposed previously for the in vivo lactonization of statin hydroxy acids...
  65. ncbi request reprint Screening of drug candidates for their drug--drug interaction potential
    A D Rodrigues
    Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, West Point, Pennsylvania 19486, USA
    Curr Opin Chem Biol 5:396-401. 2001
    ..These so called 'in silico--in vitro' correlations have great potential and may complement existing 'in vitro--in vivo' correlations...
  66. ncbi request reprint Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization
    Thomayant Prueksaritanont
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Drug Metab Dispos 30:505-12. 2002
    ....
  67. ncbi request reprint A combinatorial library of indinavir analogues and its in vitro and in vivo studies
    Yuan Cheng
    Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
    Bioorg Med Chem Lett 12:529-32. 2002
    ..The pharmacokinetics of the library was evaluated by dosing in dogs. Compounds that are notably more potent than indinavir and have favorable pharmacokinetic properties were identified...
  68. ncbi request reprint Design and synthesis of a pro-drug of vinblastine targeted at treatment of prostate cancer with enhanced efficacy and reduced systemic toxicity
    Stephen F Brady
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Med Chem 45:4706-15. 2002
    ..Additional data from metabolism studies on 5 support the supervention of a novel in vivo processing mechanism, the spontaneous release of 1b from a dipeptidyl intermediate driven by favorable diketopiperazine formation...
  69. ncbi request reprint Interindividual variability in inhibition and induction of cytochrome P450 enzymes
    J H Lin
    Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Annu Rev Pharmacol Toxicol 41:535-67. 2001
    ..This review examines the sources that are responsible for the interindividual variability in inhibition and induction of cytochrome P450 enzymes...
  70. ncbi request reprint Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact more than protein binding
    Cuyue Tang
    Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486 0004, USA
    Drug Metab Dispos 30:648-54. 2002
    ..For a given P450 reaction, therefore, the effect of BSA may depend upon enzyme affinity, catalytic capacity, and the extent of protein binding...
  71. ncbi request reprint Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine
    S K Balani
    Department of Drug Metabolism Merck Research Laboratories West Point, Pennsylvania, USA
    Drug Metab Dispos 28:1274-8. 2000
    ..Thus, the major urinary and plasma metabolites of MK-0991 resulted from peptide hydrolysis and/or N-acetylation...
  72. ncbi request reprint Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats
    J H Lin
    Merck, Sharp and Dohme Research Laboratories, West Point, Pennsylvania
    J Pharmacol Exp Ther 246:896-901. 1988
    ..This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids.(ABSTRACT TRUNCATED AT 250 WORDS)..
  73. ncbi request reprint A prostate-specific antigen (PSA)-activated vinblastine prodrug selectively kills PSA-secreting cells in vivo
    Deborah Defeo-Jones
    Mol Cancer Ther 1:451-9. 2002
    ..Similar treatment of beagle dogs with the vinblastine-conjugate showed even less toxicity. These data support the use of the PSA-hydrolyzable vinblastine-conjugate as an experimental therapy for prostate cancer in man...
  74. ncbi request reprint Cytochrome P450 in vitro reaction phenotyping: a re-evaluation of approaches used for P450 isoform identification
    Anthony Y H Lu
    Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey, USA
    Drug Metab Dispos 31:345-50. 2003
    ..Hopefully, future efforts may produce even better P450 isoform-selective marker substrates and inhibitors...
  75. ncbi request reprint Hepatic uptake of the novel antifungal agent caspofungin
    Punam Sandhu
    Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    Drug Metab Dispos 33:676-82. 2005
    ..Taken together, these findings suggest that OATP1B1-mediated hepatic uptake may contribute to the overall elimination of this drug from the body...