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

Journal Article (Journal Article)

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 equivalent results and detected hepatic and intestinal CYP3A induction and inhibition. Miosis better detected CYP3A modulation with sequential vs. simultaneous dosing. These results show that concurrent administration of oral deuterated and i.v. ALF, either sequentially or simultaneously, is an efficient and effective approach to assessing hepatic and intestinal CYP3A activity.

Full Text

Duke Authors

Cited Authors

  • Kharasch, ED; Vangveravong, S; Buck, N; London, A; Kim, T; Blood, J; Mach, RH

Published Date

  • April 2011

Published In

Volume / Issue

  • 89 / 4

Start / End Page

  • 562 - 570

PubMed ID

  • 21346758

Pubmed Central ID

  • PMC3584707

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1038/clpt.2010.313


  • eng

Conference Location

  • United States