Different effects of SLCO1B1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide
Different effects of SLCO1B1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide
复制标题
DOI：
10.1177/0091270007311569
复制
发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Niemi, Mikko
中科院分区：
文献类型：
--
作者：
Kalliokoski, Annikka;Neuvonen, Mikko;Niemi, Mikko
32名具有不同SLCO 1B 1基因型的健康志愿者摄入0.5 mg剂量的瑞格列奈和60 mg剂量的那格列奈，洗脱期为1周。SLCO 1B 1 c.521CC基因型受试者（n = 4）的平均瑞格列奈血药浓度-时间曲线下面积（AUC（0-无穷大））比c.521TC（n = 12）或c.521TT（n = 16）基因型受试者大59%（P = 0.001）或72%（P < 0.001）。瑞格列奈代谢产物M2和M4的AUC（0-无穷大）在c.521CC基因型受试者中比c.521TT基因型受试者高112%（P = 0.004）和81%（P = 0.002），但M1的药代动力学无差异。血糖浓度最大降幅与瑞格列奈AUC（0-无穷大）相关（r =0.412，P =0.019）。SLCO 1B 1基因多态性对诺格列奈及其代谢产物M7的药代动力学无显著影响。因此，与瑞格列奈相反，那格列奈的分布不受SLCO 1B 1 c.521 T>C多态性的影响。
Thirty-two healthy volunteers with different SLCO1B1 genotypes ingested a 0.5-mg dose of repaglinide and 60-mg dose of nateglinide with a washout period of 1 week. Participants with SLCO1B1 c.521CC genotype (n = 4) had a 59% (P = 0.001) or 72% (P < 0.001) greater mean area under the plasma repaglinide concentration-time curve (AUC(0-infinity)) than participants with c.521TC (n = 12) or c.521TT (n = 16) genotypes. The AUC(0-infinity) of repaglinide metabolites M2 and M4 were 112% (P = 0.004) and 81% (P = 0.002) larger in participants with c.521CC genotype than in those with c.521TT genotype, but no differences existed in the pharmacokinetics of M1. Maximum decrease in blood glucose concentration correlated with repaglinide AUC(0-infinity) (r =0.412, P =0.019). SLCO1B1 polymorphism had no significant effect on the pharmacokinetics or phormacodynamics of noteglinide or its M7 metabolite. Thus, in contrast to repaglinide, the disposition of nateglinide is unaffected by the SLCO1B1 c.521 T>C polymorphism.