3种动物经消化道给予S-多沙唑嗪甲磺酸盐与S-多沙唑嗪盐酸盐后血药浓度比较

Plasma Concentration Comparation Between S-doxazosin Mesylate and S-doxazosin Hydrochloride Administered Via Digestive System in Three Animals

目的观察3种动物经消化道给予S-多沙唑嗪甲磺酸盐和S-多沙唑嗪盐酸盐后血药浓度变化。方法将大鼠麻醉后灌胃给予S-多沙唑嗪甲磺酸盐和S-多沙唑嗪盐酸盐5.0μmol·kg^-1,观察180 min,经股静脉采血;兔麻醉后经十二指肠给予S-多沙唑嗪甲磺酸盐和S-多沙唑嗪盐酸盐,2.8μmol·kg^-1,观察120 min,经股静脉采血;猫麻醉后经十二指肠给予S-多沙唑嗪甲磺酸盐和S-多沙唑嗪盐酸盐2.0μmol·kg^-1,观察180 min,经股静脉采血。均采用高效液相色谱荧光法检测血浆药物浓度。结果大鼠给药后180 min,S-多沙唑嗪甲磺酸盐和盐酸盐的最高血药浓度分别为（51.2±31.0）和（30.6±17.5）ng·mL^-1;S-多沙唑嗪甲磺酸盐和盐酸盐在0～180 min内的浓度-时间曲线下面积之比为1.4：1。兔经十二指肠给药后120 min,S-多沙唑嗪甲磺酸盐和盐酸盐的最高血药浓度分别为（267.1±63.0）和（226.9±123.2）ng·mL^-1;S-多沙唑嗪甲磺酸盐和盐酸盐在0～120 min内的浓度-时间曲线下面积之比为1.1：1。猫经十二指肠给药后180 min,S-多沙唑嗪甲磺酸盐和盐酸盐的最高血药浓度分别是（1046.4±606.1）和（669.3±332.7）ng·mL^-1;S-多沙唑嗪甲磺酸盐和盐酸盐在0～180 min内的浓度-时间曲线下面积之比为2.4：1。结论S-多沙唑嗪甲磺酸盐经消化道吸收优于S-多沙唑嗪盐酸盐。

Objective To compare the plasma concentrations of S-doxazosin mesylate and S-doxazosin hydrochloride aderministered via digestive system in rats, rabbits and cats, respectively. Methods S-Doxazosin mesylate and S-doxazosin hydrochloride were administered via different way in three different anesthetized animals at different dose, after different time of observing, respectively, blood samples were collected via femoral vein. then the plasma drug concentrations were determined by using a high performance liquid chromatograpy （HPLC） assay. Results The maximum plasma concentration for S-doxazosin mesylate was （ 51.2 ± 31.0） ng· mL^-1 , and that for S-doxazosin hydrochloride was （30.6 ±17.5 ） ng· mL^-1 180 min after p. o. S-doxazosin mesylate and S-doxazosin hydrochloride in rats. The ratio of AUC for S-doxazosin mesylate over hydrochloride within 0- 180 min was 1.4 ： 1. The maximum plasma concentration for S-doxazosin mesylate and hydrochloride was （267.1 ± 63.0） and （226.9 ± 123.2） ng· mL^-1 , respectively, 120 min after intraduodenal administration of drugs in rabbits. The ratio of AUC for S-doxazosin mesylate over hydrochloride within 0 - 120 min was 1.1 ： 1. The maximum plasma concentration for S-doxazosin mesylate and hydrochloride was （1 046.4± 606.1 ）and （669.3 ± 332.7） ng· mL^-1 ,respectively, 180 min after intraduodenal administration in cats. The ratio of AUC for S-doxazosin mesylate over S-doxazosin hydrochloride within 0 - 180 min was 2.4 ： 1. Conclusion The results indicate that the absorption of S-doxazosin mesylate administered via digestive system is better than that of S-doxazosin hydrochloride.