利福平对健康受试者中那格列奈药代动力学和药效学的影响。
Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects.
作者信息
Niemi Mikko, Backman Janne T, Neuvonen Mikko, Neuvonen Pertti J
机构信息
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
出版信息
Br J Clin Pharmacol. 2003 Oct;56(4):427-32. doi: 10.1046/j.1365-2125.2003.01884.x.
AIMS
Our aim was to investigate the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide, a novel short-acting antidiabetic drug.
METHODS
In a randomized crossover study with two phases, 10 healthy volunteers took 600 mg rifampicin or placebo orally once daily for 5 days. On day 6 of both phases, they ingested a single 60 mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 7 h postdose.
RESULTS
Rifampicin decreased the mean AUC(0,7 h) of nateglinide by 24% (range 5-53%; P = 0.0009) and shortened its half-life (t(1/2)) from 1.6 to 1.3 h (P = 0.001). However, the peak plasma nateglinide concentration (Cmax) remained unchanged. The AUC(0,7 h) of the M7 metabolite of nateglinide was decreased by 19% (P = 0.002) and its t(1/2) was shortened from 2.1 to 1.6 h by rifampicin (P = 0.008). Rifampicin had no significant effect on the blood glucose-lowering effect of nateglinide.
CONCLUSIONS
Rifampicin modestly decreased the plasma concentrations of nateglinide probably by inducing its oxidative biotransformation. In some patients, rifampicin may reduce the blood glucose-lowering effect of nateglinide.
目的
我们的目的是研究利福平对新型短效抗糖尿病药物那格列奈的药代动力学和药效学的影响。
方法
在一项分两个阶段的随机交叉研究中，10名健康志愿者每天口服600毫克利福平或安慰剂，持续5天。在两个阶段的第6天，他们服用了单次60毫克剂量的那格列奈。给药后长达7小时测量血浆那格列奈和血糖浓度。
结果
利福平使那格列奈的平均AUC(0,7 h)降低了24%（范围为5%-53%；P = 0.0009），并将其半衰期（t(1/2)）从1.6小时缩短至1.3小时（P = 0.001）。然而，那格列奈的血浆峰值浓度（Cmax）保持不变。利福平使那格列奈的M7代谢物的AUC(0,7 h)降低了19%（P = 0.002），其t(1/2)从2.1小时缩短至1.6小时（P = 0.008）。利福平对那格列奈的降糖效果没有显著影响。
结论
利福平可能通过诱导那格列奈的氧化生物转化适度降低其血浆浓度。在一些患者中，利福平可能会降低那格列奈的降糖效果。
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