Abstract

Studies will continue to focus on the molecular aspects of drug interactions as described in the reports of the individual projects. Project I will be concerned with the potential interaction between rifampin and warfarin, rifampin and phenprocoumon, and cimetidine and warfarin in normal human subjects. Project 3 will study the metabolic fate of valproyl CoA and valproyl carnitine, the effect of valproate and delta4-valproate on fatty acid metabolism, the formation of unsaturated metabolites of valproate in general, the mechanism of inhibition of carbamazepine-10,11-epoxide and the inhibitory effect of valproate on the formation of p-hydroxyphenobarbital. Project 4 will examine the hepatoprotective effect of ethanol infused in rats and determine the value of KI in """"""""in vitro"""""""" studies. Work on the adriamycin-acetaminophen interaction will begin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM032165-03
Application #
3096181
Study Section
Pharmacology-Toxicology Review Committee (PTR)
Project Start
1983-08-01
Project End
1988-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Pharmacy
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Wong, Timothy; Wang, Zhican; Chapron, Brian D et al. (2018) Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans. Drug Metab Dispos 46:367-379
Shirasaka, Y; Chaudhry, A S; McDonald, M et al. (2016) Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content. Pharmacogenomics J 16:375-87
Manoj, Kelath Murali; Parashar, Abhinav; Gade, Sudeep K et al. (2016) Functioning of Microsomal Cytochrome P450s: Murburn Concept Explains the Metabolism of Xenobiotics in Hepatocytes. Front Pharmacol 7:161
Stamper, Brendan D; Garcia, Michael L; Nguyen, Duy Q et al. (2015) p53 Contributes to Differentiating Gene Expression Following Exposure to Acetaminophen and Its Less Hepatotoxic Regioisomer Both In Vitro and In Vivo. Gene Regul Syst Bio 9:1-14
McDonald, Matthew G; Au, Nicholas T; Rettie, Allan E (2015) P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms. Drug Metab Dispos 43:1661-9
Chaudhry, Amarjit S; Prasad, Bhagwat; Shirasaka, Yoshiyuki et al. (2015) The CYP2C19 Intron 2 Branch Point SNP is the Ancestral Polymorphism Contributing to the Poor Metabolizer Phenotype in Livers with CYP2C19*35 and CYP2C19*2 Alleles. Drug Metab Dispos 43:1226-35
Liu, Li; Collier, Ann C; Link, Jeanne M et al. (2015) Modulation of P-glycoprotein at the Human Blood-Brain Barrier by Quinidine or Rifampin Treatment: A Positron Emission Tomography Imaging Study. Drug Metab Dispos 43:1795-804
Ho, Han Kiat; Chan, James Chun Yip; Hardy, Klarissa D et al. (2015) Mechanism-based inactivation of CYP450 enzymes: a case study of lapatinib. Drug Metab Rev 47:21-8
Chapron, Brian; Risler, Linda; Phillips, Brian et al. (2015) Reversible, time-dependent inhibition of CYP3A-mediated metabolism of midazolam and tacrolimus by telaprevir in human liver microsomes. J Pharm Pharm Sci 18:101-11
Hsiao, Peng; Unadkat, Jashvant D (2014) Predicting the outer boundaries of P-glycoprotein (P-gp)-based drug interactions at the human blood-brain barrier based on rat studies. Mol Pharm 11:436-44

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