黄豆苷元对不同基因型健康受试者他林洛尔药代动力学的影响  

Effects of daidzein on pharmacokinetics of Talinolol in healthy subjects with different genotypes

作　　者：肖昌琼[1] 陈锐[1] 

机构地区：[1]郴州市第一人民医院中心医院药剂科,湖南郴州423000

出　　处：《中华生物医学工程杂志》2016年第3期244-248,共5页Chinese Journal of Biomedical Engineering

基　　金：邯州市第一人民医院院级科研课题（N2015-013）;湘南学院科研课题项目（2015XB44）

摘　　要：目的：阐明黄豆苷元在体内对不同P-糖蛋白转运体（P-gp）基因型健康受试者他林洛尔药代动力学的影响。方法基因分型筛选18例MDR1第3435位CC，CT和TT基因型健康受试者，每个基因型各6例。临床试验按照两阶段交叉方案进行。第一阶段随机分成的2组受试者给予黄豆苷元片或安慰剂处理14d，第15d给所有受试者他林洛尔，经过14 d洗脱期后交叉重复试验，分别以0、0.25、0.5、0.75、1、1.5、2、2.5、3、4、6、8、12、24、36 h为时间点抽取血样，并利用高效液相色谱法测定血样中他林洛尔的药代动力学参数。结果经黄豆苷元处理后，MDR1第3435位CC，CT和TT基因型受试者他林洛尔0-36小时曲线下面积（AUC0-36h）明显降低（P〈0.05）[（2171.14±400.28）ng.h/ml比（2448.35±55.4）ng·h/ml，（2379.27±308.14）ng·h/ml比（2571.16±30.26）ng·h/ml，（2071.16±302.14）ng·h/ml比（2588.67±45.40）ng·h/ml]；0-∞曲线下面积（AUC0-∞）显著降低（P〈0.05）[（2672.49±256.32）ng·h/ml比（2929.48±82.61）ng · h/ml，（2615.96±274.21）ng · h/ml比（2886.43±35.62）ng · h/ml，（2771.49±256.32）ng·h/ml比（2975.21±44.31）ng·h/ml]，消除半衰期（ T1/2）显著缩短（P〈0.05）[（11.81±6.96）h比（16.01±3.68）h，（9.69±2.87）h比（13.59±5.99）h]，但是对MDR1第3435位不同基因型受试者之间他林洛尔的药代动力学没有显著影响。他林洛尔的药代动力学参数AUC0-36 h、AUC0-∞、峰浓度Cmax、达峰时间Tmax和T1/2在不同MDR1基因型受试者中差异没有统计学意义。结论黄豆苷元对健康受试者他林洛尔的代谢具有显著的影响作用，他林洛尔的药代动力学不受MDR1第3435位基因型的影响。Objective To determine the in vivo effects of daidzein on pharmacokineticsof Talinolol in healthy subjectswith different P-glycoprotein（P-gp）genotypes. Methods Eighteen subjects with the genotypes of MDR1-3435 CC,CT and TT were included in the study（n=6 each）. A 2-period crossover study was conducted inthe clinical experiment. All subjects at the first periodwere randomly divided into two groups and given daidzein tablets or placebo for 14d. All subjects were given Talinolol at 15 d. A repeated and crossover experiment was conducted after a washout period of 14 d. The blood samples were collected at 0, 0.25,0.5,0.75,1,1.5,2,2.5,3,4,6,8,12,24,and 36 h,respectively. The pharmacokinetic parameters of Talinololin the blood samples were determined by high performance liquid chromatography. Results After treated by daidzein,the Talinolol 0-36h area under curve （AUC0-36 h） in patients with MDR1-3435CC,CT and TT genotypes were significantly decreased（P〈0.05）[（2 171.14±400.28）ng·h/ml vs（2 448.35 ± 55.4）ng · h/ml,（2 379.27 ± 308.14）ng · h/ml vs（2 571.16 ± 30.26）ng · h/ml,（2 071.16 ± 302.14）ng · h/ml vs（2 588.67 ± 45.40）ng · h/ml];and the AUC0-∞were significantly decreased（P〈0.05） [（2 672.49 ± 256.32）ng · .h/ml vs（2 929.48 ± 82.61）ng · h/ml,（2 615.96 ± 274.21）ng · h/ml vs（2 886.43 ± 35.62）ng·h/ml,（2 771.49±256.32）ng·h/ml vs（2 975.21±44.31）ng·h/ml]. The elimination half-life（T1/2） was significatly reduced（P〈0.05）[（11.81±6.96）h vs（16.01±3.68）h,（9.69±2.87）h vs（13.59±5.99）h]. Daidzeinshowed no significant effects on pharmacokineticsof Talinolol in the subjectswith different MDR 1-3435genotypes.There were no statistically significant differences in the pharmacokinetic parameters of Talinolol AUC0-36 h,AUC0-∞,Cmax,Tmax and T1/2 among subjects with different MDR1-3435genotypes. Conclusions Daidzeinshows significanteffects on pharmacokineticsof Talinolol in healthy subjects,which is not affected byMDR1-3

关 键 词：黄豆 药代动力学 基因型 

分 类 号：R969.1[医药卫生—药理学]