Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride

Abstract

Aims: To study the effects of rifampicin on the pharmacokinetics and pharmaco-dynamics of glimepiride, a new sulphonylurea antidiabetic drug.

Methods: In this randomised, two-phase cross-over study, 10 healthy volunteers were treated for 5 days with 600 mg rifampicin or placebo once daily. On day 6, a single oral dose of 1 mg glimepiride was administered. Plasma glimepiride and blood glucose concentrations were measured up to 12 h.

Results: Rifampicin decreased the mean area under the plasma concentration-time curve of glimepiride by 34% (P < 0.001) and the mean elimination half-life by 25% (P < 0.05). No significant differences in the blood glucose response to glimepiride were observed between the placebo and rifampicin phases. However, symptomatic hypoglycaemia occurred only during the placebo phase.

Conclusions: The effects of rifampicin on the pharmacokinetics of glimepiride suggest that rifampicin induced the CYP2C9-mediated metabolism of glimepiride and thereby slightly increased its systemic clearance. Because the interaction was modest and did not significantly alter the glucose-lowering effect of glimepiride in healthy volunteers, it is probably of limited clinical significance. However, in some patients the hypoglycaemic effect of glimepiride may be reduced during concomitant treatment with rifampicin.

Figure 1

Mean (s.e. mean) plasma concentrations of glimepiride in 10 healthy volunteers after a single 1 mg oral dose of glimepiride, following a 5 day pretreatment with placebo (open circles) or 600 mg rifampicin (solid circles) once daily.

Figure 2

Individual AUC values of glimepiride in 10 healthy volunteers after a single 1 mg oral dose of glimepiride, following a 5 day pretreatment with placebo or 600 mg rifampicin once daily. The broken lines indicate the five female subjects, who were all using oral contraceptive steroids.

Figure 3

Blood glucose concentrations (mean±s.e. mean) in 10 healthy volunteers after a single 1 mg oral dose of glimepiride, following a 5 day pretreatment with placebo (open circles) or 600 mg rifampicin (solid circles) once daily. A standard breakfast was served 15 min after the administration of glimepiride and a standard warm meal after 3 h.