Measurement of unbound geniposide in blood,liver,brain and bile of anesthetized rats:an application of pharmacokinetic study and its influence on acupuncture

摘要

We used the multiple microdialysis probes coupled to a validated liquid chromatographic (LC) system to determine the geniposide in blood,liver,brain and bile of anesthetized rats.The method was used to investigate the pharmacokinetics of geniposide and its influence by the treatment of acupuncture.Separation of geniposide from various biological fluids was applied to a Nova-Pak reversed-phase column (RP-C18,150mmX3.9mm i.d.;5mmm) at ambient temperature (24+-1degC).The mobile phase consists of acetonitrile-methanol-5 mM monosodium phosphate (pH 4.6;5:15:80,v/v/v),and the flow rate of the mobile phase was 1 ml min~(-1).The maximum UV absorbance for geniposide was set at a wavelength of 240 nm.Our results indicating geniposide may not penetrate the blood-brain barrier.The blood pharmacokinetic parameters suggest that the geniposide appears in a linear dose-dependent manner in the dosage range of 10-100mg kg~(-1).A system consisting of a hepato-duodenal shunt microdialysis model was used to investigate the hepatobiliary excretion of geniposide.The area under the concentration-time curve (AUC) of geniposide in bile was significantly greater than that of blood in the dosage of 10mg kg~(-1).The observations indicated active hepatobiliary excretion of geniposide.Acupuncture at Tai-Chong (international code:LIV 3) and Yang-Ling-Chuan acupuncture points (international code:GB 34) was related to the theory of Chinese medicine of liver-bile duct channel and bladder channel,respectively.These results indicate that acupuncture at these two acupoints does not affect the pharmacokinetics of geniposide in rat blood,liver and bile.However,more experimental data on acupuncture points and herbal ingredients are required for the interpretation of the acupuncture and pharmacokinetics on other drugs.