Pharmacokinetic-pharmacodynamic study on antipyretic effects of baicalin on carrageenan-induced pyrexia of rats / 中草药

ABSTRACT

Objective: Pharmacokinetic-pharmacodynamic (PK-PD) modeling is used to characterize the antipyretic effects of baicalin (BA) in rats. Methods: Twelve healthy male Sprague-Dawley (SD) rats were randomly divided into two groups, each with six. The rats in the first group were sc injected with carrageenan (1 mL per rat) alone to make the inflammation model. The rats in the second group were given BA (180 mg/kg) by ig administration after carrageenan injection. Body temperature was measured while orbital sinus blood sample was collected at different time points. The blood concentration of BA was determined by high performance liquid chromatography-mass spectrometry. PK-PD modelings were fitted with ADAPT 5.1 software. The model with advantage was selected by the fitting goodness. Results: The concentration-time curve was best and fitted by double-site absorption with enterohepatic circulaion of Pk model and the antipyretic responses of Sigmoid-Imax PD model could be well confirmed. The PK and PD models were reconnected by the antipyretogenetic inhibition with effect compartment. The fitting results indicated that the Imax of antipyretic effect by BA was 0.56 °C and shape parameter (H) for PD was 10.67. Conclusion: The dose-effect relationship range in the antipyretic activity of BA on carrageenan-induced pyrexia of rats is narrow and its efficiency is low.