替米沙坦在中国健康志愿者体内的药代动力学特征

Pharmacokinetic characteristics of telmisartan in Chinese healthy volunteers

目的 通过对健康志愿者口服不同剂量替米沙坦片后的药代动力学研究 ,探讨替米沙坦在国人体内的药代动力学特征。方法 9名中国健康男性志愿者按拉丁方设计分别口服三种单剂量替米沙坦片 (4 0、80、12 0mg) ,用高效液相色谱荧光检测法测定血浆替米沙坦浓度 ,采用 3P97软件拟合药代动力学参数。结果 受试者血药浓度随其单剂量给药量的增加呈现非比例的升高趋势 ,计算所得的药动学参数显示 ,口服 4 0、80、12 0mg替米沙坦片的AUC0～ 96分别为(895 0 3± 36 4 5 3)、(30 30 34± 14 5 4 80 )和 (135 70 4 4±35 5 1 5 4 ) μg·h-1·L-1;Cmax 分别为 (6 0 71± 2 8 10 )、(2 14 0 5± 74 14 )和 (978 32± 2 34 89) μg·L-1,不同剂量组的AUC0 t/dose、Cmax/Dose比值间差异有显著性 (P <收稿日期 :2 0 0 4-0 4-2 6,修回日期 :2 0 0 4-0 5 -2 9作者简介 :熊玉卿 ( 195 7-) ,女 ,博士 ,教授 ,研究方向 :药物代谢及药代动力学 ,Tel:0 791 63 60 65 4,E mail:xyq112 6@yahoo .com .cn0 0 1)。结论 替米沙坦在中国人体内过程 (剂量范围为 4 0～ 12 0mg)

Objective To explore the pharmacokinetic characteristics of telmisartan in Chinese healthy volunteers. Methods 9 Chinese male healthy volunteers were divided into receiving orally a single dose of 40, 80, 120 mg telmisartan tablets respectively, in latin square design study. After administration of telmisartan tablets, the plasma concentration was determined by HPLC with fluorescent detection. The pharmacokinetic parameters were analyzed by 3P97 program. Results It was found that plasma levels increased after orally increased dosages of telmisartan in the healthy volunteers in a nor-dose-dependent manner. The pharmacokinetic parameters were calculated the follows: AUC 0-96 of three different dosages (40, 80,120 mg) were (895.03±364.53), ( 3 030.34± 1 454.80) and ( 13 570.44± 3 551.54) μg·h -1·L -1; and C max were (60.71±28.10), (214.05±74.14) and (978.32±234.89) μg·L -1. There were significant differences in AUC 0-t/dose, C max/dose between the groups (P<0.01). Conclusion The pharmacokinetic characteristics of telmisartan in Chinese healthy volunteers (in 40～120 mg process) were fitted with non-linear kinetic model.