Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Ethnopharmacol. 2013 Jul 9;148(2):617-23. doi: 10.1016/j.jep.2013.05.013. Epub 2013 May 21.
Salvianolic acid A (SAA) is one of the main water-soluble components isolated from Salvia miltiorrhiza Bunge. Pharmacological researches revealed that it had various curative activities after oral and intravenous administration, including beneficial effects on diabetes and its complications, cardioprotective effect, anti-platelet aggregation, and so on. However, there is no report regarding the pharmacokinetics of SAA in beagle dogs after oral administration up to now.
To study the pharmacokinetics of different doses of SAA in beagle dogs and figure out the absolute bioavailability and dose proportionality of SAA after oral administration.
Male and female beagle dogs were orally administered SAA 5, 10 and 20mg/kg randomly. The plasma drug concentration was detected by a rapid, sensitive and reproducible liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic parameters were calculated from plasma concentration-time data using the DAS pharmacokinetic software Data Analysis System Version 3.0 program.
After single-dose oral administration of SAA, the mean peak plasma concentration (Cmax) values for groups treated with 5, 10 and 20 mg/kg doses ranged from 14.38 to 38.18 µg/L, and the mean area under the concentration-time curve (AUC(0-t)) values ranged from 38.77 to 130.33 (µg/L·h). SAA showed lack of dose proportionality over the dose range 5-20mg/kg, based on the power model. However, the increase in systemic exposure with dose appeared linear. The absolute bioavailability was calculated to range from 1.47% to 1.84%.
The pharmacokinetic properties of SAA in beagle dogs after oral administration were characterized as rapid oral absorption, quick clearance, and poor absolute bioavailability. Systemic exposure exhibited lack of dose proportionality over the dose range 5-20mg/kg. Furthermore, a readily preparative LC-MS method was demonstrated in this study for the research of traditional Chinese medicine.
丹酚酸 A（SAA）是从丹参中分离得到的主要水溶性成分之一。药理研究表明，它经口服和静脉给药后具有多种治疗活性，包括对糖尿病及其并发症的有益作用、心脏保护作用、抗血小板聚集等。然而，迄今为止，尚无关于 SAA 在口服给药后在比格犬体内药代动力学的报道。
研究不同剂量 SAA 在比格犬体内的药代动力学特征，确定 SAA 口服给药后的绝对生物利用度和剂量比例性。
雄性和雌性比格犬随机口服给予 SAA 5、10 和 20mg/kg。采用快速、灵敏、重现性好的液相色谱-质谱（LC-MS）法检测血浆药物浓度。采用 DAS 药代动力学软件 Data Analysis System Version 3.0 程序，根据血浆浓度-时间数据计算药代动力学参数。
单次口服 SAA 后，5、10 和 20mg/kg 剂量组的平均峰血浆浓度（Cmax）值范围为 14.38-38.18µg/L，平均浓度-时间曲线下面积（AUC（0-t））值范围为 38.77-130.33（µg/L·h）。基于幂函数模型，SAA 在 5-20mg/kg 剂量范围内表现出剂量非比例性。然而，随着剂量的增加，系统暴露呈线性增加。绝对生物利用度计算范围为 1.47%-1.84%。
比格犬口服 SAA 的药代动力学特征为快速口服吸收、快速清除和较差的绝对生物利用度。在 5-20mg/kg 剂量范围内，系统暴露表现出剂量非比例性。此外，本研究还建立了一种易于制备的 LC-MS 方法，用于研究中药。
