目的 考察杠柳毒苷iv給藥在大鼠體內(nèi)的藥動(dòng)學(xué)過(guò)程。方法 大鼠iv給予低、中、高劑量（0.37、0.74、1.48 mg/kg）杠柳毒苷后于不同時(shí)間點(diǎn)采血，血漿樣品經(jīng)甲醇沉淀蛋白-C₁₈固相萃取處理，HPLC-UV法測(cè)定不同時(shí)間點(diǎn)大鼠血漿中杠柳毒苷藥物濃度。用DAS藥動(dòng)學(xué)數(shù)據(jù)軟件計(jì)算藥動(dòng)學(xué)參數(shù)。結(jié)果 低、中、高劑量組杠柳毒苷的分布相半衰期t_1/2α分別為1.49、2.32、3.48 min，消除相半衰期t_1/2β分別為14.00、12.37、15.44 min，無(wú)顯著性差異。AUC_0-60分別為8.581、19.782、50.615 mg/L?min，與劑量呈線性相關(guān)。結(jié)論 杠柳毒苷iv給藥在大鼠體內(nèi)分布及消除迅速，其體內(nèi)過(guò)程符合二房室模型，在0.37～1.48 mg/kg符合線性動(dòng)力學(xué)過(guò)程。

Objective To investigate the in vivo pharmacokinetic properties of periplocin from Periplocae Cortex in rats after iv injection. Methods Low, medium, and high dosage of periplocin were administered to rats respectively and blood was sampled at designed time points. Plasma samples were pretreated by protein precipitation with methanol, followed by solid-phase extraction with a C₁₈ cartridge. Plasma concentrations of periplocin were determined by HPLC-UV method. Main pharmacokinetic parameters were calculated with DAS software. Results After single iv injection with doses of 0.37, 0.74, and 1.48 mg/kg to rats, t_1/2α of periplocin were 1.49, 2.32, and 3.48 min, respectively; t_1/2β were 14.00, 12.37, and 15.44 min, respectively, without significant differences. AUC_0-60 were 8.581, 19.782, and 50.615 mg/L?min, respectively. The AUCs were found to be linearly correlated with dosages. Conclusion Periplocin shows the rapid distribution and elimination in rats after iv injection. Pharmacokinetics of periplocin fits best to a two-compartment model with first order kinetics. Amount of in vivo exposure is positively correlated with dosage over the dose range of 0.37—1.48 mg/kg.

國(guó)家自然科學(xué)基金資助項(xiàng)目（30973932）；高等學(xué)校博士學(xué)科點(diǎn)專項(xiàng)科研基金資助項(xiàng)目（20070063001）