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

Publication ,  Journal Article
Kharasch, ED; Vangveravong, S; Buck, N; London, A; Kim, T; Blood, J; Mach, RH
Published in: Clin Pharmacol Ther
April 2011

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.

Duke Scholars

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

April 2011

Volume

89

Issue

4

Start / End Page

562 / 570

Location

United States

Related Subject Headings

  • Young Adult
  • Rifampin
  • Pharmacology & Pharmacy
  • Miosis
  • Male
  • Liver
  • Ketoconazole
  • Intestinal Mucosa
  • Humans
  • Female
 

Citation

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MLA
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Kharasch, E. D., Vangveravong, S., Buck, N., London, A., Kim, T., Blood, J., & Mach, R. H. (2011). Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil. Clin Pharmacol Ther, 89(4), 562–570. https://doi.org/10.1038/clpt.2010.313
Kharasch, E. D., S. Vangveravong, N. Buck, A. London, T. Kim, J. Blood, and R. H. Mach. “Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.Clin Pharmacol Ther 89, no. 4 (April 2011): 562–70. https://doi.org/10.1038/clpt.2010.313.
Kharasch ED, Vangveravong S, Buck N, London A, Kim T, Blood J, et al. Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil. Clin Pharmacol Ther. 2011 Apr;89(4):562–70.
Kharasch, E. D., et al. “Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.Clin Pharmacol Ther, vol. 89, no. 4, Apr. 2011, pp. 562–70. Pubmed, doi:10.1038/clpt.2010.313.
Kharasch ED, Vangveravong S, Buck N, London A, Kim T, Blood J, Mach RH. Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil. Clin Pharmacol Ther. 2011 Apr;89(4):562–570.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

April 2011

Volume

89

Issue

4

Start / End Page

562 / 570

Location

United States

Related Subject Headings

  • Young Adult
  • Rifampin
  • Pharmacology & Pharmacy
  • Miosis
  • Male
  • Liver
  • Ketoconazole
  • Intestinal Mucosa
  • Humans
  • Female