Kinetics of drug metabolism inhibition: Use of metabolite concentration-time profiles

Shaw, P. Nicholas and Houston, J.Brian (1987) Kinetics of drug metabolism inhibition: Use of metabolite concentration-time profiles. Journal of Pharmacokinetics and Biopharmaceutics, 15 5: 497-510. doi:10.1007/BF01061759

Author Shaw, P. Nicholas
Houston, J.Brian
Title Kinetics of drug metabolism inhibition: Use of metabolite concentration-time profiles
Journal name Journal of Pharmacokinetics and Biopharmaceutics   Check publisher's open access policy
ISSN 0090-466X
Publication date 1987-10-01
Sub-type Article (original research)
DOI 10.1007/BF01061759
Volume 15
Issue 5
Start page 497
End page 510
Total pages 14
Place of publication New York, NY, United States
Publisher Springer
Language eng
Abstract A simple model simulating the kinetics of drug metabolism inhibition interaction is investigated. The relative sensitivity of drug and metabolite concentration-time profiles as indices of inhibition is assessed. Under steady-state conditions where inhibitor concentrations are maintained constant, the determination of metabolite in addition to drug kinetics provides little additional information when inhibition is nonselective in nature. However metabolite profiles do offer increased sensitivity when parallel routes of metabolism exist and there is selectivity of inhibitory action. Non-steadystate conditions are also investigated as they often apply in inhibition studies; the inhibitor is often administered as a single dose or as a multiple dosing regimen rather than by a constant rate intravenous infusion. Under the former conditions, when inhibitor concentrations in the body fluctuate during the study, metabolite kinetics can be more useful than drug kinetics. The changes evident in the metabolite concentration-time profiles are substantial due to both the inhibition per se and the nonlinearity in the system arising from inhibitor elimination. It is concluded that metabolite kinetics provide a useful aid in the detection of drug metabolism inhibition interactions.
Keyword Drug metabolism
Metabolism inhibition interactions
Metabolite Kinetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 21 Dec 2010, 00:10:32 EST