Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.

ABSTRACT: Alfentanil (ALF) is a validated probe for hepatic, first-pass, and intestinal cytochrome P450 (CYP) 3A activity, using plasma clearances, single-point concentrations, and noninvasive pupil diameter change (miosis). Assessing intravenous (i.v.) and oral drug disposition typically requires separate dosing. This investigation evaluated concurrent administration of oral deuterated and i.v. unlabeled ALF to assess both intestinal and hepatic CYP3A, and compare sequential and simultaneous dosing. ALF disposition was evaluated after strong hepatic and/or intestinal CYP3A induction and inhibition by rifampin, ketoconazole, and grapefruit juice. Using plasma ALF concentrations and area under the curve (AUC), clearance, or single-point concentrations, both simultaneous and sequential dosing provided

SUBMITTER: Kharasch ED 

PROVIDER: S-EPMC3584707 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature