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Clinical Trial
. 2009 Jan;85(1):78-85.
doi: 10.1038/clpt.2008.186. Epub 2008 Oct 8.

Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite

H X Zheng  1 , Y Huang, L A Frassetto, L Z Benet
Affiliations
Clinical Trial

Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite

H X Zheng et al. Clin Pharmacol Ther. 2009 Jan.

Abstract

The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.

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Conflict of interest statement

Conflict of Interest

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
AUC ratios of 4-hydroxyglyburide to glyburide in nine healthy volunteers on each treatment group. * Significantly different than control (p< 0.05).
Figure 2
Figure 2
Change of blood glucose level in nine healthy volunteers on each treatment group
Figure 3
Figure 3
AUC ratios of 4-hydroxyglyburide to glyburide in nine healthy volunteers on each treatment group. * Significantly different than Control (p<0.05).
Figure 4
Figure 4
Change of blood glucose level in nine healthy volunteers on each treatment group
See this image and copyright information in PMC

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