Niemi M, Kivistö K T, Backman J T, Neuvonen P J
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Br J Clin Pharmacol. 2000 Dec;50(6):591-5. doi: 10.1046/j.1365-2125.2000.00295.x.
To study the effects of rifampicin on the pharmacokinetics and pharmaco-dynamics of glimepiride, a new sulphonylurea antidiabetic drug.
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.
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.
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.
研究利福平对新型磺酰脲类抗糖尿病药物格列美脲的药代动力学和药效学的影响。
在这项随机、两阶段交叉研究中，10名健康志愿者每天接受一次600mg利福平或安慰剂治疗，持续5天。在第6天，口服单次剂量1mg格列美脲。在12小时内测量血浆格列美脲和血糖浓度。
利福平使格列美脲的血浆浓度-时间曲线下平均面积降低34%（P<0.001），平均消除半衰期降低25%（P<0.05）。在安慰剂期和利福平期之间，未观察到格列美脲的血糖反应有显著差异。然而，有症状的低血糖仅在安慰剂期出现。
利福平对格列美脲药代动力学的影响表明，利福平诱导了CYP2C9介导的格列美脲代谢，从而略微增加了其全身清除率。由于这种相互作用较小，且未显著改变格列美脲在健康志愿者中的降糖效果，其临床意义可能有限。然而，在一些患者中，同时使用利福平时，格列美脲的降糖效果可能会降低。
