α-细辛脑经干粉吸入给药后在大鼠体内的药动学研究

Pharmacokinetic study on dry powder inhalation administration of α-asarone in rats

研究α-细辛脑经干粉吸入给药后在大鼠体内的药代动力学特征和绝对生物利用度,并与灌胃给药,静脉注射给药进行比较.建立大鼠血浆中α-细辛脑的HPLC检测方法.考察大鼠分别经干粉吸入（20 mgkg-1）,灌胃（80 mgkg-1）,静脉注射（20 mgkg-1）给予α-细辛脑后血药浓度变化.采用DAS 2.0软件计算药动学参数,根据各给药途径的AUC（0-t）及给药剂量,计算α-细辛脑经干粉吸入和灌胃后的绝对生物利用度.结果显示α-细辛脑在质量浓度为0.282~14.1 mgL-1呈良好的线性关系（r=0.999 4）;检测下限为0.212 mgL-1.大鼠经干粉吸入,灌胃和静脉注射给予α-细辛脑后,α-细辛脑在大鼠体内的代谢过程分别符合一室模型,二室模型和三室模型;消除半衰期分别为（95.4848.28）,（66.9929.76）,（64.3427.59） min.按生物利用度公式计算,α-细辛脑经干粉吸入给药和灌胃给药后绝对生物利用度分别为78.32%,33.60%.研究表明采用干粉吸入方式给药可延长α-细辛脑药物消除半衰期并显著提高绝对生物利用度,为其干粉吸入剂的制备打下了理论基础.

To study the pharmacokinetic characteristics and absolute bioavailability of α-asarone through dry powder inhalation in rats, and compare with that through oral administration and intravenous injection. A HPLC method was established for the determination of α-asarone in rat plasma to detect the changes in plasma concentrations of α-asarone through dry powder inhalation （20 mgkg-1）, oral administration （80 mgkg-1） and intravenous injection （20 mgkg-1） in rats. DAS 2.0 software was used to calculate the pharmacokinetic parameters. The absolute bioavailability of α-asarone was calculated according to AUC（0-t） of administration routes and administration doses. According to the results, α-asarone showed good linear relations （r=0.999 4） at concentrations between 0.282-14.1 mgL-1, with the limit of detection （LOD） at 0.212 mgL-1. Through dry powder inhalation, oral administration and intravenous injection of α-asarone, the metabolic processes of α-asarone in rats conformed to one, two and three compartment models respectively, with the elimination half-life of （95.4848.28）, （64.3427.59）, （66.9929.76） min. According to the bioavailability formula, the absolute bioavailability of α-asarone through dry powder inhalation and oral administration were 78.32% and 33.60%, respectively. This study showed that significant increase in elimination half-life and absolute bioavailability of α-asarone through dry powder inhalation, which lays a theoretical foundation for preparing α-asarone dry powder inhalers.keywords：α-asarone