Abstract

The objectives of the applicant's proposed research, which build on her work and accomplishments during fellowship, are: l. To develop and apply a model of in vitro drug metabolism by human and animal liver microsomal preparations to identify specific cytochrome subfamilies mediating biotransformation of a number of psychotropic drugs, and to identify potential inhibitors of metabolism; 2. Using index or probe reactions identified as being mediated by specific cytochrome subfamilies, together with immunochemical and molecular genetic methods, to assess the effects of age and gender on activity and quantity of specific cytochromes; 3. To assess the influence of age and gender on the susceptibility to metabolic inhibition by chemical inhibitors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Scientist Development Award (K21)
Project #
5K21MH001237-03
Application #
2415776
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Project Start
1995-09-15
Project End
2000-04-30
Budget Start
1997-06-01
Budget End
1998-04-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Venkatakrishnan, K; von Moltke, L L; Greenblatt, D J (2001) Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther 297:326-37
Hesse, L M; Venkatakrishnan, K; Court, M H et al. (2000) CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 28:1176-83
Greenblatt, D J; von Moltke, L L; Harmatz, J S et al. (1999) Human cytochromes mediating sertraline biotransformation: seeking attribution. J Clin Psychopharmacol 19:489-93
Greenblatt, D J; Wright, C E; von Moltke, L L et al. (1998) Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences. Clin Pharmacol Ther 64:237-47
Greenblatt, D J; Harmatz, J S; von Moltke, L L et al. (1998) Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther 64:553-61
Schmider, J; Greenblatt, D J; von Moltke, L L et al. (1997) Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: studies of phenytoin p-hydroxylation. Br J Clin Pharmacol 44:495-8
Schmider, J; Greenblatt, D J; Fogelman, S M et al. (1997) Metabolism of dextromethorphan in vitro: involvement of cytochromes P450 2D6 and 3A3/4, with a possible role of 2E1. Biopharm Drug Dispos 18:227-40
Schmider, J; Greenblatt, D J; von Moltke, L L et al. (1997) Biotransformation of mestranol to ethinyl estradiol in vitro: the role of cytochrome P-450 2C9 and metabolic inhibitors. J Clin Pharmacol 37:193-200
Charpentier, K P; von Moltke, L L; Poku, J W et al. (1997) Alprazolam hydroxylation by mouse liver microsomes in vitro: the effect of age and phenobarbital induction. Biopharm Drug Dispos 18:139-49
Schmider, J; Greenblatt, D J; von Moltke, L L et al. (1996) Inhibition of cytochrome P450 by nefazodone in vitro: studies of dextromethorphan O- and N-demethylation. Br J Clin Pharmacol 41:339-43

Showing the most recent 10 out of 12 publications