Pharmacokinetic-pharmacodynamic study on antipyreticeffects of coptisine on endotoxin-induced pyrexia of rats / 中国药理学通报

ABSTRACT

Aim To establish the pharmacokinetic-pharmacodynamic(PK-PD) modeling to characterize the antipyretic effects of coptisine, an active component in coptis chinensis on rats.Methods Nine healthy male Sprague-Dawley(SD) rats were randomly divided into three groups, each with three.The rats in the first group were injected intravenously with lipopolysaccharide(LPS,100 μg·kg-1) alone.The second and third group rats were given coptisine high-dose(3.87 mg·kg-1) and coptisine low-dose(1.93 mg·kg-1) by tail vein injection at 30 min after LPS injection, respectively.Body temperature was measured at different time points, and blood samples from tail vein were collected simultaneously.The blood concentration of coptisine was determined by ultra performance liquid chromatography.Monolix software was used to model PK-PD of coptisine mean plasma concentration and temperature effects,by population computation with non-covariates.Besides.the model with advantage was selected by the fitting goodness.Results Coptisine could inhibit body temperature of endotoxin-induced fever in rats significantly.Two-compartment linear elimination model was used to describe the final PK model.Gaussian function, an input function of body temperature changes, which was used to depict PD model, the PK and PD models were connected by the Emax model.At last, the final model was fitted better;the fitting results indicated that the EC50 of antipyretic effect of coptisine was 89.7 μg·L-1, and the Emax was 1.88℃.Conclusions Coptisine has a powerful anti-pyretic effect on endotoxin-induced pyrexia of rats with high potency, Low in vivo distribution and quick clearance.