R S Obach

Summary

Affiliation: Pfizer Global Research and Development
Country: USA

Publications

  1. ncbi request reprint Nonspecific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol
    R S Obach
    Department of Drug Metabolism, Pfizer Central Research, Groton, CT 06340, USA
    Drug Metab Dispos 25:1359-69. 1997
  2. ncbi request reprint Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes
    R S Obach
    Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer, Inc, Groton, Connecticut 06340, USA
    Drug Metab Dispos 27:1350-9. 1999
  3. ncbi request reprint Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression
    R S Obach
    Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer, Inc, Groton, Connecticut 06340, USA
    J Pharmacol Exp Ther 294:88-95. 2000
  4. ncbi request reprint Metabolism of ezlopitant, a nonpeptidic substance P receptor antagonist, in liver microsomes: enzyme kinetics, cytochrome P450 isoform identity, and in vitro-in vivo correlation
    R S Obach
    Drug Metabolism Department, Pfizer Central Research, Groton, CT 06340, USA
    Drug Metab Dispos 28:1069-76. 2000
  5. ncbi request reprint Mechanism of cytochrome P4503A4- and 2D6-catalyzed dehydrogenation of ezlopitant as probed with isotope effects using five deuterated analogs
    R S Obach
    Department of Drug Metabolism, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Drug Metab Dispos 29:1599-607. 2001
  6. ncbi request reprint Three-dimensional quantitative structure activity relationship computational approaches for prediction of human in vitro intrinsic clearance
    S Ekins
    Central Research Division, Pfizer Inc, Groton, Connecticut
    J Pharmacol Exp Ther 295:463-73. 2000
  7. ncbi request reprint (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes
    J M Margolis
    Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer Inc, Groton, Connecticut, USA
    Drug Metab Dispos 28:1187-91. 2000
  8. ncbi request reprint Expression and characterization of canine cytochrome P450 2D15
    F Roussel
    Drug Metabolism Department, Molecular Sciences Department, Pfizer Inc, Eastern Point Road, Groton, Connecticut 06340, USA
    Arch Biochem Biophys 357:27-36. 1998
  9. ncbi request reprint Cytochrome P450-catalyzed metabolism of ezlopitant alkene (CJ-12,458), a pharmacologically active metabolite of ezlopitant: enzyme kinetics and mechanism of an alkene hydration reaction
    R S Obach
    Drug Metabolism, Pfizer, Inc, Groton, Connecticut
    Drug Metab Dispos 29:1057-67. 2001
  10. ncbi request reprint Mechanism-based inactivation of human cytochrome P450 enzymes: strategies for diagnosis and drug-drug interaction risk assessment
    K Venkatakrishnan
    Clinical Pharmacology, Pfizer Global Research and Development, MS8260 2626, EasternPoint Road, Groton, CT 06340, USA
    Xenobiotica 37:1225-56. 2007

Detail Information

Publications13

  1. ncbi request reprint Nonspecific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol
    R S Obach
    Department of Drug Metabolism, Pfizer Central Research, Groton, CT 06340, USA
    Drug Metab Dispos 25:1359-69. 1997
    ..Furthermore, the extent of nonspecific binding to microsomes is likely an important parameter to consider when attempting to relate Ki values measured in vitro to observations of drug-drug interactions (or the lack thereof) in vivo...
  2. ncbi request reprint Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes
    R S Obach
    Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer, Inc, Groton, Connecticut 06340, USA
    Drug Metab Dispos 27:1350-9. 1999
    ..Overall, inclusion of both blood and microsome binding values gave the best agreement between in vivo clearance values and clearance values projected from in vitro intrinsic clearance data...
  3. ncbi request reprint Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression
    R S Obach
    Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer, Inc, Groton, Connecticut 06340, USA
    J Pharmacol Exp Ther 294:88-95. 2000
    ....
  4. ncbi request reprint Metabolism of ezlopitant, a nonpeptidic substance P receptor antagonist, in liver microsomes: enzyme kinetics, cytochrome P450 isoform identity, and in vitro-in vivo correlation
    R S Obach
    Drug Metabolism Department, Pfizer Central Research, Groton, CT 06340, USA
    Drug Metab Dispos 28:1069-76. 2000
    ..The apparent predominance of CYP3A over CYP2D6 is consistent with observations of the pharmacokinetics of ezlopitant in humans in vivo...
  5. ncbi request reprint Mechanism of cytochrome P4503A4- and 2D6-catalyzed dehydrogenation of ezlopitant as probed with isotope effects using five deuterated analogs
    R S Obach
    Department of Drug Metabolism, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Drug Metab Dispos 29:1599-607. 2001
    ..8 to 5.9. Thus, dehydrogenation does not appear to occur via enzyme-mediated general acid catalysis of the benzyl alcohol. A mechanism for the dehydrogenation of ezlopitant is proposed in consideration of the data presented...
  6. ncbi request reprint Three-dimensional quantitative structure activity relationship computational approaches for prediction of human in vitro intrinsic clearance
    S Ekins
    Central Research Division, Pfizer Inc, Groton, Connecticut
    J Pharmacol Exp Ther 295:463-73. 2000
    ..These present models represent a preliminary application of QSAR software to modeling and prediction of human in vitro intrinsic clearance...
  7. ncbi request reprint (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes
    J M Margolis
    Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer Inc, Groton, Connecticut, USA
    Drug Metab Dispos 28:1187-91. 2000
    ..Together, these findings suggest a significant role for the polymorphically expressed CYP2D6 in fluoxetine clearance and are consistent with reports on the clinical pharmacokinetics of fluoxetine...
  8. ncbi request reprint Expression and characterization of canine cytochrome P450 2D15
    F Roussel
    Drug Metabolism Department, Molecular Sciences Department, Pfizer Inc, Eastern Point Road, Groton, Connecticut 06340, USA
    Arch Biochem Biophys 357:27-36. 1998
    ..Thus, the dog expresses a CYP2D ortholog possessing enzymatic activities similar to human CYP2D6, but is affected by the inhibitors quinine and quinidine in a manner closer to that of rat CYP2D1...
  9. ncbi request reprint Cytochrome P450-catalyzed metabolism of ezlopitant alkene (CJ-12,458), a pharmacologically active metabolite of ezlopitant: enzyme kinetics and mechanism of an alkene hydration reaction
    R S Obach
    Drug Metabolism, Pfizer, Inc, Groton, Connecticut
    Drug Metab Dispos 29:1057-67. 2001
    ..From these data, a mechanism for this reaction is proposed involving epoxidation, an exocyclic hydride shift, and reduction at the benzylic position...
  10. ncbi request reprint Mechanism-based inactivation of human cytochrome P450 enzymes: strategies for diagnosis and drug-drug interaction risk assessment
    K Venkatakrishnan
    Clinical Pharmacology, Pfizer Global Research and Development, MS8260 2626, EasternPoint Road, Groton, CT 06340, USA
    Xenobiotica 37:1225-56. 2007
    ....
  11. doi request reprint Understanding the clinical pharmacokinetics of a GABAA partial agonist by application of in vitro tools
    Aarti D Sawant
    Department of Pharmacokinetics, Pharmacodynamics and Metabolism, Pfizer Global Research and Development, Groton New London Laboratories, Pfizer Inc, Groton, CT 06340, USA
    Xenobiotica 40:476-84. 2010
    ....
  12. ncbi request reprint The prediction of human clearance from hepatic microsomal metabolism data
    R S Obach
    Drug Metabolism Department, Pfizer Inc, Groton, CT 06340, USA
    Curr Opin Drug Discov Devel 4:36-44. 2001
    ....
  13. ncbi request reprint Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro-in vivo study
    B Feng
    Department of Pharmacokinetics, Pharmacodynamics, Drug Metabolism, Pfizer Global Research and Development, Groton, Connecticut, USA
    Clin Pharmacol Ther 83:567-76. 2008
    ..Consequently, it can be reasonably expected that other inhibitors of hOCT2 would not cause greater renal interactions with varenicline than that seen with the efficient hOCT2 inhibitor cimetidine...