Relationship Between Extent of Inhibition and Inhibitor Dose: Literature Evaluation Based on the Metabolism and Transport Drug Interaction Database

Title: Relationship Between Extent of Inhibition and Inhibitor Dose: Literature Evaluation Based on the Metabolism and Transport Drug Interaction Database

Volume: 4 Issue: 5

Author(s): R. H. Levy, H. Hachad, C. Yao and I. Ragueneau-Majlessi

Affiliation:

Keywords: Cytochrome P450,, drug interaction,, dose-dependent inhibition,, mechanism-based inhibition,

Abstract: A comprehensive search of the literature was undertaken using the Metabolism and Transport Drug Interaction Database (http: / / depts.washington.edu / didbase / ) to evaluate the relationship between extent of inhibition and inhibitor dose. The search included reversible and irreversible inhibitors in studies conducted in the period 1966-2003. Only twelve inhibitors met the criterion of the search: study population exposed to more than one dose of inhibitor within a given study design. Six were reversible inhibitors: ciprofloxacin, enoxacin, felbamate, fluconazole, fluvoxamine and ketoconazole. The other six (cimetidine, diltiazem, disulfiram, paroxetine, verapamil and ritonavir) are considered irreversible inhibitors. Most of the AUC / Clearance data available for both types of inhibitors suggested evidence of dose-dependent inhibition. In the case of reversible inhibitors, the evidence of dose-dependent inhibition is consistent with a number of recent studies suggesting the determination of in vivo inhibition constants based on plasma concentration of inhibitor.

Cite this article as:

Levy H. R., Hachad H., Yao C. and Ragueneau-Majlessi I., Relationship Between Extent of Inhibition and Inhibitor Dose: Literature Evaluation Based on the Metabolism and Transport Drug Interaction Database, Current Drug Metabolism 2003; 4 (5) . https://dx.doi.org/10.2174/1389200033489325