关键词: 大黄酸, SD大鼠, Beagle犬, 体内吸收, 血浆药物浓度, 药代动力学HPLC-荧光检测法

Abstract: 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.

Key words: Rhein, SD rat, Beagle dog, Absorption in vivo, Plasma concentration, Pharmacokinetics, HPLC-Fluorescence