Niemi M, Backman J T, Neuvonen M, Neuvonen P J, Kivistö K T
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Finland.
Clin Pharmacol Ther. 2000 Nov;68(5):495-500. doi: 10.1067/mcp.2000.111183.
To study the effects of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of repaglinide, a new short-acting antidiabetic drug.
In a randomized, two-phase crossover study, nine healthy volunteers were given a 5-day pretreatment with 600 mg rifampin or matched placebo once daily. On day 6 a single 0.5-mg dose of repaglinide was administered. Plasma repaglinide and blood glucose concentrations were measured up to 7 hours.
Rifampin decreased the total area under the concentration-time curve of repaglinide by 57% (P < .001) and the peak plasma repaglinide concentration by 41% (P = .001). The elimination half-life of repaglinide was shortened from 1.5 to 1.1 hours (P < .01). The blood glucose decremental area under the concentration-time curve from 0 to 3 hours was reduced from 0.94 to -0.23 mmol/L x h (P < .05), and the maximum decrease in blood glucose concentration from 1.6 to 1.0 mmol/L (P < .05) by rifampin.
Rifampin considerably decreases the plasma concentrations of repaglinide and also reduces its effects. This interaction is probably caused by induction of the CYP3A4-mediated metabolism of repaglinide. It is probable that the effects of repaglinide are decreased during treatment with rifampin or other potent inducers of CYP3A4, such as carbamazepine, phenytoin, or St John's wort.
研究利福平（国际非专利药品名称，利福平）对新型短效抗糖尿病药物瑞格列奈的药代动力学和药效学的影响。
在一项随机、两阶段交叉研究中，9名健康志愿者接受为期5天的预处理，每天一次服用600mg利福平或匹配的安慰剂。在第6天给予单次0.5mg剂量的瑞格列奈。测量长达7小时的血浆瑞格列奈和血糖浓度。
利福平使瑞格列奈浓度-时间曲线下的总面积降低了57%（P <.001），血浆瑞格列奈峰值浓度降低了41%（P =.001）。瑞格列奈的消除半衰期从1.5小时缩短至1.1小时（P <.01）。利福平使0至3小时浓度-时间曲线下的血糖降低面积从0.94降至-0.23 mmol/L×h（P <.05），血糖浓度的最大降幅从1.6降至1.0 mmol/L（P <.05）。
利福平显著降低瑞格列奈的血浆浓度，并降低其药效。这种相互作用可能是由CYP3A4介导的瑞格列奈代谢诱导引起的。在使用利福平或其他强效CYP3A4诱导剂（如卡马西平、苯妥英或圣约翰草）治疗期间，瑞格列奈的药效可能会降低。
