| Rhodiola rosea L.(family Crassulaceae), the most important species of the genus Rhodiola, is known as a "source of adaptation to the environment", and have anti-hypoxia, anti-aging, anti-diabetes, enhance immune function, anti-hepatic fibrosis. The main active constituents are salidroside, tyrosol and etc. In this study, we evaluated the absorption, metabolism, excretion of salidroside in rats.(1) Absorption:The healthy male Wistar rats were divided into oral group and intravenous group (each group was administrated 50mg·kg-1 salidroside, and then the plasma salidroside concentrations were determined at different times. The pharmacokinetic parameters were calculated with non-compartment model of WinNonlin pharmacokinetic software based on time-blood concentration data. The results shown that bioavailability of Salidroside after oral administration is 28.74%, indicated that it has a low bioavailability.To explore the reasons of low bioavailability, we examined penetration study of salidroside in the Caco-2 cell monolayer as the transport model for the absorption of the drug. The concentration of salidroside in the apical side (AP) and basolateral side (BL) were determined, then apparent permeability coefficient (Papp) and the efflux rate (Pratio) were calculated based on AP and BL. The Papp from AP to BL and from BL to AP are (1.41±0.27)×10-5cm/s, (3.48±0.43)×10-5cm/s respectively, and the Pratio is 2.47. The result shows that an active efflux mechanism may contribute to low absorption of salidroside in the intestinal tract.(2) Metabolism:Healthy male Wistar rats were divided into acute liver injury group and the normal treatment group (each group was given 50mg·kg-1 salidroside intraveneouslly). The plasma salidroside concentrations were measured at different times after salidroside administration, then the pharmacokinetic parameters were calculated with non-compartment model of WinNonlin pharmacokinetic software based on time-blood concentration data. The results are as follows:Acute liver injury group:t1/2 (0.60±0.03) h; CL (0.53±0.03) L·h-1; V(0.43±0.01) L;AUC0-∞(93.62±5.52)μg·h·mL-1; MRT (0.87±0.05) h. The normal treatment group:t1/2(0.37±0.06) h; CL (1.23±0.15)L·h-1; V(0.61=0.06) L;AUC0-∞(41.35±4.91)μg·h·mL-1; MRT(0.42±0.07) h. There were si-gnificant difference between two groups in t1/2,CL, V, MRT, and AUC0-∞(P＜0.05), and the results indicate that salidroside is partially metabolized by liver.(3) Excretion:Healthy male Wistar rat collected urine for 24 hours after intra-gastric administration of salidroside (50mg·kg-1), and then the urine also collected at different time after intravenous injection of salidroside (50mg·kg-1) in the same rat. The content of salidroside in the urine sample was determined by HPLC method. The total elimination rate constant (K), renal elimination rate constant (Ke), and renal excretion rate of salidroside were calculated based on urine content of salidroside. The result shows as follow: K=(0.573±0.08) h-1, Ke=(0.293±0.08) h-1, renal excretion rate= 50.40%. The results indicate that salidroside mainly eliminated through kidney with original drug.It is concluded that (1) an active efflux mechanism probably contribute to low absorption of salidroside in the intestinal tract; (2) salidroside is mainly eliminated by kidney with original drug, and partially metabolized by liver.The results will provide scientific basis for new drug design, preparation development and dosage form in vivo evaluation and clinical applications. |
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