大黄酸在大鼠和比格犬体内的吸收动力学研究

目的：研究中药大黄的活性蒽醌单体大黄酸（rhein）在SD大鼠和Beagle犬体内的吸收动力学特征,为临床的进一步研究提供基础参数和依据。方法：采用HPLC-荧光检测法分别测定SD大鼠和Beagle犬在灌胃及静脉注射两种给药途径下单次给予不同剂量的大黄酸药物后,两种动物血浆样品中的大黄酸经时曲线过程并计算相应的药代动力学参数及绝对生物利用度。结果：SD大鼠灌胃及静脉注射高、中、低剂量大黄酸后,AUC与剂量间呈一定的线性关系（r〉0.99）,灌胃及静脉注射3个剂量下的半衰期结果相似。在上述研究范围内大黄酸在大鼠体内的药代动力学行为近似是线性的。用面积法,算得高、中、低3个剂量下大黄酸在大鼠体内的绝对生物利用度分别为16.4%、23.8%、19.4%。对6只Beagle犬进行随机交叉试验,静脉注射大黄酸真溶液（0.4mg/kg）和灌胃大黄酸混悬液（20mg/kg）,算得静注及灌胃后药物的消除半衰期分别为（1.77±0.93）、（3.25±0.80）h,Beagle犬体内的绝对生物利用度为（49.7±7.4）%。对Beagle犬组（6只）和SD大鼠灌胃3剂量组（18只）各只动物生物利用度进行方差分析,结果显示差异具有统计学意义（P〈0.01）。结论：大黄酸在不同动物间吸收存在一定的种属差异,吸收程度在Bea-gle犬体内略高于在大鼠体内。

Pharmacokinetic comparision in absorption of Rhein in SD rats and Beagle dogs

AIM：An in vivo study was conducted to evaluate the pharmacokinetic profile of Rhein （an anthraquinone derivatives isolated from chinese rhubarab） in plasma of SD rats and Beagle dogs. METHODS：Using a rapid and sensitive HPLC-Fluorescence mothod to determine the plasma concentration of rhein after a single i.v. and i.g. administration to SD rats and Beagle dogs at different dosages. A representative plasma concentration vs time profile was illustrated,and the PK parameters and absolute bioavailability were calculated based on these results. RESULTS：After a single i.g. administration and a single i.v. injection of rhein at high,middle and low dosages to rats,there was a good linear relationship between the AUC and dosage （r〉0.99）. The estimated half life of rhein had some similarities in three different dosage of i.g. administration and i.v. injection. These indicated a linearity pharmacokinetic behavior of rhein in the studied dosage range. The oral bioavailability of rhein in SD rats of high、middle and low dosages were 16.4%,23.8% and 19.4%,respectively. The pharmacokinetic profiles of rhein to six Beagle dogs show that：after a single i.v. administration of 0.4 mg/kg,and i.g. administration of 20 mg/kg,the estimated half life of rhein were （1.77±0.93） h and （3.25±0.80） h,respectively. However,the oral absolute bioavailability of rhein in Beagle dogs was （49.7±7.4）%. Analysis the subject bioavailability data of each Beagle dog （n=6） and each rat in three oral dosage groups （n=18）,showed a statistically significant difference （P〈0.01） between this two groups. CONCLUSION：There are some species differences between dogs and rats in absorption behavior.The absorption in dogs is higher than in rats.