吲达帕胺对大鼠替米沙坦药代动力学的影响及性别差异(英文)

目的研究吲达帕胺对雌性和雄性大鼠替米沙坦药代动力学的影响。方法Wistar大鼠随机分为替米沙坦单用和替米沙坦与吲哒帕胺联用组,雌雄各半,分别单次ig给予替米沙坦3.6mg·kg-1或替米沙坦3.6mg·kg-1+吲达帕胺0.135mg·kg-1。96h内定时取血后,采用反相高效液相色谱-荧光检测法测定血浆中替米沙坦浓度。结果无论雄性雌性大鼠,与替米沙坦单用组相比,联用吲达帕胺后替米沙坦的主要药代动力学参数无显著性改变;而不同性别大鼠替米沙坦的药代动力学有显著差异,无论替米沙坦单用或联用吲达帕胺组,雌性大鼠替米沙坦的主要药代动力学参数AUC和cmax值均显著高于雄性,而血浆清除率显著低于雄性。结论替米沙坦与吲达帕胺联用对大鼠替米沙坦的药代动力学无明显影响;而无论替米沙坦单用或联用吲达帕胺,雌性和雄性大鼠替米沙坦的药代动力学存在显著的性别差异。

Influence of indapamide on pharmacokinetics of telmisartan in male and female rats

AIM To study the influence of indapamide(Ind) on pharmacokinetics of telmisartan(Tel) and observe the difference between male and female rats. METHODS Wistar rats were divided into Tel and Tel+Ind groups, each group containing 8 female and 8 male rats, and were ig administered a single dose of either Tel 3.6 mg·kg^-1 or Tel 3.6 mg·kg^-1+Ind 0.135 mg·kg^-1, respectively. Blood samples were collected at intervals over 96 h after administration. The Tel concentrations in plasma were determined by high performance liquid chromatography with fluorescence detector. The Tel concentration-time curves were simulated by 3p97 software and the pharmacokinetic parameters were calculated. RESULTS Whatever in female or male rats, there were no significant differences in the main pharmacokinetic parameters of Tel between Tel and Tel+Ind groups. However, females had higher values for area under the concentration-time curve and maximum plasma concentration than males, but lower values for total clearance in both Tel and Tel+Ind groups. CONCLUSION Ind has no significant influences on the pharmacokinetics of Tel. However, pharmacokinetics of Tel is significant different between male and female rats.