论文部分内容阅读
目的:研究异绿原酸A在大鼠体内的生物利用度和药代动力学,为该制剂的临床应用提供参考。方法:建立大鼠血浆中异绿原酸A的HPLC检测,检测波长300 nm,流动相甲醇-0.1%磷酸水(50∶50)。考察大鼠经静脉注射(32 mg·kg-1)与灌胃(90 mg·kg-1)给予异绿原酸A后的血药浓度变化,利用3P97软件计算药动学参数,根据药时曲线下面积AUC0-∞和给药剂量,计算异绿原酸A的绝对生物利用度。结果:异绿原酸A在0.16~110.00 mg·L-1线性良好(R2=0.998);质量浓度分别为0.43,6.88,55.00 mg·L-1的异绿原酸A的提取回收率分别为(89.43±2.84)%,(93.16±3.95)%,(85.91±2.04)%;日内精密度RSD分别为11.8%,4.0%,4.0%,日间精密度RSD分别为6.5%,5.8%,5.8%。大鼠静脉注射和灌胃异绿原酸A后,异绿原酸A在大鼠体内的代谢过程均符合二室模型,消除半衰期分别为(29.49±0.75),(44.48±0.13)min,AUC0-∞分别为(355.40±32.58),(319.91±51.00)mg·min-1·L-1。异绿原酸A在大鼠体内的绝对生物利用度30.71%。结论:异绿原酸A在大鼠体内的过程符合线性动力学过程,且代谢快、半衰期短。
OBJECTIVE: To study the bioavailability and pharmacokinetics of chlorogenic acid A in rats and provide a reference for its clinical application. Methods: The HPLC method was established for the determination of chlorogenic acid A in rat plasma. The detection wavelength was 300 nm and the mobile phase consisted of methanol - 0.1% phosphoric acid (50:50). The change of plasma concentration of chlorogenic acid after intravenous injection (32 mg · kg -1) and gavage (90 mg · kg -1) in rats was investigated. Pharmacokinetic parameters were calculated by 3P97 software. The area under the curve, AUC0-∞, and the dose administered calculated the absolute bioavailability of isocrochloric acid A. Results: The linear range of iso-chlorogenic acid A was 0.16-110.00 mg · L-1 (R2 = 0.998). The recoveries of iso-chlorogenic acid A with mass concentrations of 0.43, 6.88 and 55.00 mg · L- (RSD) were (89.43 ± 2.84)%, (93.16 ± 3.95)% and (85.91 ± 2.04)%, respectively. Intravenous precision RSD was 11.8%, 4.0% and 4.0% %. After intravenous administration of isocrochloride A and the intragastric administration of iso-chlorogenic acid A, the metabolic process of iso-chlorogenic acid A in rats was in accordance with the two-compartment model with the elimination half-life of (29.49 ± 0.75), (44.48 ± 0.13) min and AUC0 -∞ were (355.40 ± 32.58) and (319.91 ± 51.00) mg · min-1 · L-1, respectively. The absolute bioavailability of chlorogenic acid A in rats was 30.71%. CONCLUSION: The process of iso-chlorogenic acid A in rats is in accordance with the linear kinetic process with fast metabolism and short half-life.