TIMOTHY TRACY

Summary

Affiliation: University of Minnesota
Country: USA

Publications

  1. ncbi request reprint Modeling kinetic data from in vitro drug metabolism enzyme experiments
    Timothy S Tracy
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Drug Metab Rev 36:231-42. 2004
  2. pmc CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis
    Murali Subramanian
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55126, USA
    Drug Metab Dispos 37:1682-9. 2009
  3. ncbi request reprint Atypical enzyme kinetics: their effect on in vitro-in vivo pharmacokinetic predictions and drug interactions
    Timothy S Tracy
    Dept of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, USA
    Curr Drug Metab 4:341-6. 2003
  4. ncbi request reprint Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy
    Timothy S Tracy
    Department of Experimental and Clinical Pharmacology and Center of Excellence in Women s Health, University of Minnesota, Minneapolis, Minn, USA
    Am J Obstet Gynecol 192:633-9. 2005
  5. ncbi request reprint Atypical cytochrome p450 kinetics: implications for drug discovery
    Timothy S Tracy
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Drugs R D 7:349-63. 2006
  6. ncbi request reprint Activation of CYP2C9-mediated metabolism by a series of dapsone analogs: kinetics and structural requirements
    J Matthew Hutzler
    Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, USA
    Drug Metab Dispos 30:1194-200. 2002
  7. ncbi request reprint Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles
    Timothy S Tracy
    Deparment of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, USA
    Drug Metab Dispos 30:385-90. 2002
  8. ncbi request reprint Visible spectra of type II cytochrome P450-drug complexes: evidence that "incomplete" heme coordination is common
    Charles W Locuson
    Department of Experimental and Clinical Pharmacology, University of Minnesota, College of Pharmacy, 7 115B Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA
    Drug Metab Dispos 35:614-22. 2007
  9. ncbi request reprint Inhibition of CYP2D6 activity by bupropion
    Michael Kotlyar
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Twin Cities Campus, Minneapolis, MN 55455, USA
    J Clin Psychopharmacol 25:226-9. 2005
  10. ncbi request reprint Differential activation of CYP2C9 variants by dapsone
    Matthew A Hummel
    Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV, USA
    Biochem Pharmacol 67:1831-41. 2004

Research Grants

Collaborators

Detail Information

Publications36

  1. ncbi request reprint Modeling kinetic data from in vitro drug metabolism enzyme experiments
    Timothy S Tracy
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Drug Metab Rev 36:231-42. 2004
    ..This article briefly summarizes the types of equations necessary to adequately model both typical and atypical kinetic profiles in order to facilitate correct estimation of the relevant kinetic parameters...
  2. pmc CYP2D6-CYP2C9 protein-protein interactions and isoform-selective effects on substrate binding and catalysis
    Murali Subramanian
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN 55126, USA
    Drug Metab Dispos 37:1682-9. 2009
    ..In summary, CYP2C9-CYP2D6 interactions can alter catalytic activity and, thus, influence in vitro-in vivo correlation predictions...
  3. ncbi request reprint Atypical enzyme kinetics: their effect on in vitro-in vivo pharmacokinetic predictions and drug interactions
    Timothy S Tracy
    Dept of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, USA
    Curr Drug Metab 4:341-6. 2003
    ..Furthermore, potential, artifactual causes of atypical kinetic phenomena will be described...
  4. ncbi request reprint Temporal changes in drug metabolism (CYP1A2, CYP2D6 and CYP3A Activity) during pregnancy
    Timothy S Tracy
    Department of Experimental and Clinical Pharmacology and Center of Excellence in Women s Health, University of Minnesota, Minneapolis, Minn, USA
    Am J Obstet Gynecol 192:633-9. 2005
    ..The purpose of this study was to determine whether drug metabolism (CYP1A2, CYP2D6 and CYP3A) activity varies in the pregnant state compared with the nonpregnant state...
  5. ncbi request reprint Atypical cytochrome p450 kinetics: implications for drug discovery
    Timothy S Tracy
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Drugs R D 7:349-63. 2006
    ..Thus, the clinical relevance of these phenomena remains inconclusive...
  6. ncbi request reprint Activation of CYP2C9-mediated metabolism by a series of dapsone analogs: kinetics and structural requirements
    J Matthew Hutzler
    Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, USA
    Drug Metab Dispos 30:1194-200. 2002
    ..However, the effects of these analogs appear to be concentration- and substrate-dependent, further complicating the prediction of these types of in vitro interactions...
  7. ncbi request reprint Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles
    Timothy S Tracy
    Deparment of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, USA
    Drug Metab Dispos 30:385-90. 2002
    ..It seems that the kinetic profile of CYP2C9-mediated metabolism is dependent on both substrate and the CYP2C9 allelic variant, thus having potential ramifications on drug disposition predictions made during the development process...
  8. ncbi request reprint Visible spectra of type II cytochrome P450-drug complexes: evidence that "incomplete" heme coordination is common
    Charles W Locuson
    Department of Experimental and Clinical Pharmacology, University of Minnesota, College of Pharmacy, 7 115B Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA
    Drug Metab Dispos 35:614-22. 2007
    ..Therefore, difference spectra may help reveal "weak" coordination to the heme that results from suboptimal orientation or ligand binding to more remote locations within the P450 active sites...
  9. ncbi request reprint Inhibition of CYP2D6 activity by bupropion
    Michael Kotlyar
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Twin Cities Campus, Minneapolis, MN 55455, USA
    J Clin Psychopharmacol 25:226-9. 2005
    ..Bupropion is therefore a potent inhibitor of CYP2D6 activity, and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6...
  10. ncbi request reprint Differential activation of CYP2C9 variants by dapsone
    Matthew A Hummel
    Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV, USA
    Biochem Pharmacol 67:1831-41. 2004
    ..Thus, amino acid substitutions of CYP2C9 variants affect the degree of dapsone activation in a genotype-dependent fashion. Furthermore, the degree of effect noted across variants appeared to be dependent on the substrate studied...
  11. pmc Substrate proton to heme distances in CYP2C9 allelic variants and alterations by the heterotropic activator, dapsone
    Matthew A Hummel
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 7 115B Weaver Densford Hall, 308 Harvard Street, SE, Minneapolis, MN 55455, USA
    Arch Biochem Biophys 475:175-83. 2008
    ....
  12. pmc CYP2C9 protein interactions with cytochrome b(5): effects on the coupling of catalysis
    Charles W Locuson
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
    Drug Metab Dispos 35:1174-81. 2007
    ..Together, these findings suggest that cyt b5 can alter multiple steps in the P450 catalytic cycle via complex interactions with P450 and P450 reductase...
  13. pmc Correlation between bilirubin glucuronidation and estradiol-3-gluronidation in the presence of model UDP-glucuronosyltransferase 1A1 substrates/inhibitors
    Jin Zhou
    Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
    Drug Metab Dispos 39:322-9. 2011
    ..Thus, estradiol-3-glucuronidation can serve as a good surrogate for predicting inhibition of bilirubin glucuronidation with the caveat that occasionally compounds may demonstrate activation of estradiol-3-glucuronidation...
  14. pmc Differential genotype dependent inhibition of CYP2C9 in humans
    Vikas Kumar
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
    Drug Metab Dispos 36:1242-8. 2008
    ..In summary, the presence of CYP2C9(*)3 alleles (either one or two alleles) can alter the degree of drug interaction observed upon coadministration of inhibitors...
  15. pmc Use of simple docking methods to screen a virtual library for heteroactivators of cytochrome P450 2C9
    Charles W Locuson
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Med Chem 50:1158-65. 2007
    ..One of the top-scoring compounds identified was verified to be a CYP2C9 heteroactivator in vitro, and it possessed activity similar to dapsone...
  16. ncbi request reprint Studying cytochrome P450 kinetics in drug metabolism
    Melissa A Kramer
    University of Minnesota, College of Pharmacy, Department of Experimental and Clinical Pharmacology, 7 115B Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA
    Expert Opin Drug Metab Toxicol 4:591-603. 2008
    ....
  17. pmc Enzyme source effects on CYP2C9 kinetics and inhibition
    Vikas Kumar
    Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA
    Drug Metab Dispos 34:1903-8. 2006
    ..Considering these differences, consistent use of an enzyme source is an important component in producing comparable and reproducible kinetics and inhibition data with CYP2C9...
  18. ncbi request reprint Amiodarone analog-dependent effects on CYP2C9-mediated metabolism and kinetic profiles
    Vikas Kumar
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
    Drug Metab Dispos 34:1688-96. 2006
    ..In addition, these kinetics effects are concentration- and genotype-dependent...
  19. ncbi request reprint CYP2C-catalyzed delta9-tetrahydrocannabinol metabolism: kinetics, pharmacogenetics and interaction with phenytoin
    Tina M Bland
    Department of Basic Pharmaceutical Sciences, School of Pharmacy, P O Box 9530, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA
    Biochem Pharmacol 70:1096-103. 2005
    ..These in vitro data suggest the potential for an interaction from the concomitant administration of delta9-THC and phenytoin that could result in decreased phenytoin concentrations in vivo...
  20. pmc Preparation, characterization, and substrate metabolism of gold-immobilized cytochrome P450 2C9
    Peter M Gannett
    Basic Pharmaceutical Sciences, West Virginia University, P O Box 9530, Morgantown, WV 26506, USA
    J Am Chem Soc 128:8374-5. 2006
    ..Most significantly, conditions that allow measurable CYP2C9 metabolism to occur have been developed...
  21. pmc CYP2C9 genotype-dependent effects on in vitro drug-drug interactions: switching of benzbromarone effect from inhibition to activation in the CYP2C9.3 variant
    Matthew A Hummel
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 308 Harvard St, S E, Minneapolis, MN 55455, USA
    Mol Pharmacol 68:644-51. 2005
    ..3 not only reduces metabolism compared with CYP2C9.1 but can also dramatically alter inhibitor effects, suggesting that differential degrees of drug inhibition interactions may occur in individuals with this variant form of CYP2C9...
  22. ncbi request reprint Atypical kinetic profiles in drug metabolism reactions
    J Matthew Hutzler
    Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, USA
    Drug Metab Dispos 30:355-62. 2002
  23. pmc Polymorphic variants of CYP2C9: mechanisms involved in reduced catalytic activity
    Lian Wei
    Department of Experimental and Clinical Pharmacology, University of Minnesota, 308 Harvard St SE, Minneapolis, MN 55455, USA
    Mol Pharmacol 72:1280-8. 2007
    ..These results suggest that in addition to coupling differences, differential uncoupling to shunt products and differences in spin state help explain the reduced catalytic activity in these enzymes...
  24. ncbi request reprint Epoxidation of the methamphetamine pyrolysis product, trans-phenylpropene, to trans-phenylpropylene oxide by CYP enzymes and stereoselective glutathione adduct formation
    Madhu Sanga
    Department of Basic Pharmaceutical Sciences, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA
    Toxicol Appl Pharmacol 211:148-56. 2006
    ..Exposure of cultured C6 glial cells to (S,S)-phenylpropylene oxide produced a cytotoxic response in a concentration-dependent manner based on cell degeneration and death...
  25. ncbi request reprint Influence of fluorescent probe size and cytochrome b5 on drug-drug interactions in CYP2C9
    Matthew A Hummel
    Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, USA
    J Biomol Screen 11:303-9. 2006
    ..These results illustrate that multiple substrate probes may be necessary for screening drug-drug interaction in CYP2C9 and that cyt b5 effects can impart steric restraints on the CYP2C9 active site...
  26. ncbi request reprint Heteroactivator effects on the coupling and spin state equilibrium of CYP2C9
    Charles W Locuson
    University of Minnesota, Department of Experimental and Clinical Pharmacology, USA
    Arch Biochem Biophys 449:115-29. 2006
    ....
  27. ncbi request reprint CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles
    Vikas Kumar
    Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA
    Drug Metab Dispos 34:1966-75. 2006
    ..Thus, both genotype and choice of probe substrate must be considered when attempting to predict potential CYP2C9 drug-drug interactions from in vitro data...
  28. pmc Glucuronidation of dihydrotestosterone and trans-androsterone by recombinant UDP-glucuronosyltransferase (UGT) 1A4: evidence for multiple UGT1A4 aglycone binding sites
    Jin Zhou
    Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Drug Metab Dispos 38:431-40. 2010
    ..Our results suggest that multiple aglycone binding sites exist within UGT1A4, which may result in atypical kinetics (both homotropic and heterotropic) in a substrate-dependent fashion...
  29. pmc Electrocatalytic drug metabolism by CYP2C9 bonded to a self-assembled monolayer-modified electrode
    Mingli Yang
    West Virginia University, Basic Pharmaceutical Sciences, Morgantown, WV 26506 9530, USA
    Drug Metab Dispos 37:892-9. 2009
    ..Furthermore, this system may provide a unique platform for both studying P450 enzyme electrochemistry and as a bioreactor to produce metabolites without the need for expensive redox transfer proteins and cofactors...
  30. ncbi request reprint Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures
    Bernard J Komoroski
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Drug Metab Dispos 32:512-8. 2004
    ....
  31. ncbi request reprint Identification of binding sites of non-I-helix water molecules in mammalian cytochromes p450
    Charles W Locuson
    Department of Experimental and Clinical Pharmacology, University of Minnesota, College of Pharmacy, Minneapolis, Minnesota, USA
    Drug Metab Dispos 34:1954-7. 2006
    ....
  32. ncbi request reprint Alterations in drug disposition during pregnancy: implications for drug therapy
    Lucy S Hodge
    University of Minnesota, Department of Experimental and Clinical Pharmacology, College of Pharmacy, Minneapolis, MN 55455, USA
    Expert Opin Drug Metab Toxicol 3:557-71. 2007
    ..As such, pregnant women may require different dosing regimens than both men and non-pregnant women...
  33. pmc CYP2C9-CYP3A4 protein-protein interactions: role of the hydrophobic N terminus
    Murali Subramanian
    Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55126, USA
    Drug Metab Dispos 38:1003-9. 2010
    ..These results show that the N-terminal membrane binding domains of CYP2C9 and CYP3A4 are involved in heteromer complex formation and that at least one consequence is a reduction in CYP2C9 activity...
  34. ncbi request reprint Validation of incorporating flurbiprofen into the Pittsburgh cocktail
    Nathalie K Zgheib
    Center for Clinical Pharmacology, University of Pittsburgh, Pittsburgh, PA 15219 3138, USA
    Clin Pharmacol Ther 80:257-63. 2006
    ..This study evaluated the possibility of incorporating flurbiprofen into the current 5-drug Pittsburgh cocktail...
  35. ncbi request reprint Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations
    J Matthew Hutzler
    Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Health Sciences Center, HSN, Morgantown, WV 26506, USA
    Arch Biochem Biophys 410:16-24. 2003
    ....
  36. ncbi request reprint Effector-mediated alteration of substrate orientation in cytochrome P450 2C9
    Matthew A Hummel
    Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, West Virginia 26506, USA
    Biochemistry 43:7207-14. 2004
    ..Shift of the 4' proton of flurbiprofen closer to the heme iron of CYP2C9 in the presence of dapsone may play a role in activation...

Research Grants14

  1. P450 Protein-Protein Interactions Determined by Selective Protein Manipulation
    TIMOTHY TRACY; Fiscal Year: 2009
    ..abstract_text> ..
  2. Pharmacogenetics and Drug Interactions
    TIMOTHY TRACY; Fiscal Year: 2007
    ..these studies will permit a better understanding of drug inhibition potential in different P450 genotypes and serve as a foundation for increasing our understanding of interindividual differences in susceptibility to drug interactions ..
  3. Mechanisms of Atypical Drug Kinetics and Interactions
    TIMOTHY TRACY; Fiscal Year: 2007
    ..From these data, computer models will be developed to predict the occurrence of atypical kinetics and potential drug interactions to assist in the drug development process. ..
  4. PharmGKB Experimental Biology Workshop 2005
    TIMOTHY TRACY; Fiscal Year: 2005
    ....
  5. Mechanisms of Atypical Drug Kinetics and Interactions
    TIMOTHY TRACY; Fiscal Year: 2003
    ..Additionally, in vivo studies of a CYP2C9 substrate and a known (in vitro) effector will be conducted. Taken together, these results will improve CYP2C9 in vitro-in vivo predictive capabilities. ..
  6. Pharmacogenetics and Drug Interactions
    TIMOTHY TRACY; Fiscal Year: 2009
    ..Improved understanding of these genetic changes and their effects on drug disposition will lead to improved drug therapy and better management of drug-drug interactions. ..