CYP2D6*10基因多态性与比索洛尔药动学关系研究

Reliationship of CYP2D6*10 Genetic Polymorphisms with the Pharmacokinetics of Bisoprolol

目的:研究CYP2D6*10不同基因型对健康志愿者体内比索洛尔药动学的影响。方法:采用实时荧光测序法分析CYP2D6*10基因型。将24例健康志愿者分为CC、CT、TT基因型3组(n=8),受试者单剂量口服富马酸比索洛尔片5 mg后,采用高效液相色谱法测定血药浓度。结果:CC、CT、TT 3种基因型受试者之间主要药动学参数t1/2、cmax、AUC0-32 h分别为(8.25±1.80)、(7.70±1.18)、(8.19±1.86)h,(41.69±11.22)、(37.69±6.53)、(43.14±5.85)μg/L,(394.38±104.70)、(380.04±84.04)、(414.08±104.40)μg·h/L。通过t检验,3种基因型之间无显著性差异(P>0.05)。结论:比索洛尔药动学在个体间的差异与CYP2D6*10基因型无相关性。

OBJECTIVE：To study the effects of different CYP2D6＊10 genotypes on pharmacokinetics of bisoprolol in the healthy volunteers.METHODS：CYP2D6＊10 genotypes were determined by real-time PCR.24 healthy subjects were divided into CC genotype group,CT genotype group and TT genotype group（n=8）.All the subjects were administered with Bisoprolol fumarate tablets at a single oral dose of 5 mg.Plasma concentration of bisoprolol was measured by HPLC.RESULTS：The main pharmacokinetic parameters of 3 genotypes of CC,CT and TT were as follows：t1/2（8.25±1.80）h,（7.70±1.18）h and（8.19±1.86）h;cmax（41.69±11.22）μg/L,（37.69±6.53）μg/L and（43.14±5.85）μg/L;AUC0-32 h（394.38±104.70）μg·h/L,（380.04±84.04）μg·h/ L and（414.08±104.40）μg·h/L.There was no significant differences among 3 genotypes by t-test（P0.05）.CONCLUSIONS： The individual differences of bisoprolol pharmacokinetics are not related with CYP2D6＊10 genotypes.