隐丹参酮及其代谢物在猪体内的药代动力学研究

PHARMACOKINETICS OF CRYPTOTANSHINONE AND ITS METABOLITE IN PIGS

目的：研究隐丹参酮（ＣＴ）及其代谢物丹参酮ＩＡ（ＴＳ）在猪体内的药代动力学。方法：实验猪５头，单剂量（１０ｍｇ·ｋｇ－１）ｉｖ隐丹参酮后，采用反相ＨＰＬＣ法检测ＣＴ及ＴＳ的血浆浓度。以二苄基为内标，流动相为甲醇—水（８５∶１５），检测波长２５４ｎｍ。结果：ＣＴ血药时程符合二室开放模型。ｉｍ与ｐｏ给药后，ＣＴ和ＴＳ的血药浓度很低。少量原药及其代谢产物在胆汁中随着给药时间的延长逐渐增多。不同途径给药后（ｉｖ及ｐｏ），隐丹参酮及丹参酮ＩＡ在尿中的排泄量占给药剂量的比例很小。

AIM: To study the pharmacokinetics and excretion of the antibacterial constituent cryptotanshinone (CT) isolated from the roots of Saliva przewaalskii Maxim (Labiatae) and its metabolite tanshinone IIA(TS) in pigs. METHODS: Normal pigs were given CT iv 10 mg·kg -1 . The concentrations of CT and TS in porcine plasma, urine and bile were determined by an HPLC method developed in our laberatory. A waters model 480 instrument was used throughout the experiment. Dibenyl was used as the internal standard at absorption wavelength of 254 nm. A mixture of methanol and water(85∶15) was used as the mobile phase with a flow rate of 1 ml·min -1 , and YWG C 18 H 37 as stationary phase. RESULTS: The method is simple, sensitive and available for pharmacokinetics studies. Plasma drug concentration time course of CT after iv adminstration of CT was found to be fitted to a two compartment open model and its pharmacokinetic paremeters were as follows: T 1/2α =2 36 min, T 1/2β =64 78 min, AUC=23 83 mg·min·L -1 . TS was detected simultaneously. Peak plasma concentration of TS was reached at about 4 6 minutes after dosing. C max =0 62 μg·ml -1 , T 1/2β =189 04 min, AUC=22 97 mg·min·L -1 . The excretion of CT and TS in urine and bile in 24～48 hour was very few after iv and po administration of CT. CONCLUSION: The pharmacokinetics of CT and TS in pigs provided a useful index for clinical trial in animals.