摘要
OBJECTIVE: To study the daily administration times of Canhuang tablet(CHT) for treating jaundice in rats based on a pharmacodynamic/ pharmacokinetic model.METHODS: Rats were modeled by 4% 1-Naphthylisothiocyanate(75 mg/kg, p.o.). After 48 h, CHT was given(p.o.) at 0.75 g/kg once a day, 0.375 g/kg twice a day, and 0.25 g/kg three times a day. Blood was collected from the orbital sinus at different intervals. Levels of liver enzymes and bilirubin were detected using these blood samples. Bile was collected and determined after the first administration of CHT. High-performance liquid chromatography was used to determine the concentration of berberine in bile simultaneously. Time-effect and time-dose curves were then obtained.RESULTS: Compared with rats taking CHT twiceand three times a day, the total amount of bile within 10 h of rats taking CHT once a day were 1.32-and 1.47-fold higher, respectively. There was good consistency between the pharmacokinetics of berberine and the pharmacodynamics of the effect on liver enzymes and bilirubin in vivo. The pharmacokinetic analyses showed that rats administered CHT once daily maintained a higher concentration of berberine in bile for a longer period than rats administered CHT two- and three-times daily.CONCLUSION: In jaundiced rats, taking CHT once a day is better than taking CHT twice or three times a day. These data may provide a reference for the clinical application of CHT.
OBJECTIVE： To study the daily administration times of Canhuang tablet （CHT） for treating jaundice in rats based on a pharmacodynamic/pharma- cokinetic model. METHODS： Rats were modeled by 4% 1-Naphthylisothiocyanate （75 mg/kg, p.o.）. After 48 h, CHT was given （p.o.） at 0.75 g/kg once a day, 0.375 g/kg twice a day, and 0.25 g/kg three times a day. Blood was collected from the orbital sinus at different intervals. Levels of liver enzymes and bilirubin were detected using these blood samples. Bile was collected and determined after the first administration of CHT. High-performance liquid chromatography was used to determine the concentration of berberine in bile simultaneously. Time-effect and time-dose curves were then obtained.RESULTS： Compared with rats taking CHT twice and three times a day, the total amount of bile with- in 10 h of rats taking CHT once a day were 1.32- and 1.47-fold higher, respectively. There was good consistency between the pharmacokinetics of berberine and the pharmacodynamics of the effect on liver enzymes and bilirubin in vivo. The pharmacokinetic analyses showed that rats administered CHT once daily maintained a higher concentration of berberine in bile for a longer period than rats administered CHT twoand three-times daily. CONCLUSION： In jaundiced rats, taking CHT once a day is better than taking CHT twice or three times a day. These data may provide a reference for the clinical application of CHT.
基金
Supported by the Shibingshiyao Program of Beijing Municipal Science and Technology Commission(No.Z131100002513005)
