Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride.
OBJECTIVE
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.
Niemi
M
M
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Kivistö
K T
KT
Backman
J T
JT
Neuvonen
P J
PJ
D000328:Adult; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D012293:Rifampin / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000097:blood / Q000493:pharmacokinetics*
D000904:Antibiotics, Antitubercular; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D012293:Rifampin