Zhu Jie, Song Min, Tan Hong-Yi, Huang Li-Hua, Huang Zhi-Jun, Liu Chang, Fu Zhi-Min, Huang Yuan-Yuan, Tan Zhi-Rong, Chen Xiao-Ping, Yuan Hong, Yang Guo-Ping
Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Pak J Pharm Sci. 2013 May;26(3):577-84.
The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration (Cmax) of repaglinide (P=0.003) in SLCO1B11b homozygotes (P=0.015) and SLCO1B115 carriers (P=0.031). Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity (AUC0⇒∞) of repaglinide (P=0.091). There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the Cmax of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported.
研究了匹伐他汀和SLCO1B1基因背景对瑞格列奈药代动力学和药效学特性的影响。在这项随机、安慰剂对照、交叉研究中，12名健康中国男性每天服用4mg匹伐他汀或安慰剂，持续5天，然后在第5天口服4mg瑞格列奈。分别采用液相色谱-串联质谱法（LC/MS/MS）和葡萄糖氧化酶法测定血浆瑞格列奈和葡萄糖水平。在SLCO1B11b纯合子（P=0.015）和SLCO1B115携带者（P=0.031）中，匹伐他汀治疗显著提高了瑞格列奈的血浆峰浓度（Cmax）（P=0.003）。匹伐他汀治疗使瑞格列奈从0小时到无穷大的血浆浓度-时间曲线下面积（AUC0⇒∞）略有增加（P=0.091）。在匹伐他汀组或对照组中，SLCO1B1各基因型之间瑞格列奈的药代动力学参数或降糖效果均无显著差异。匹伐他汀以依赖SLCO1B1基因型的方式增加瑞格列奈的血浆Cmax，但对健康志愿者中瑞格列奈的药效学无明显影响。该陈述的P值未报告。
