Dose-dependent pharmacokinetics of bulleyaconitine A in rats

This study was conducted to determine the pharmacokinetic characteristics of bulleyaconitine A (BLA) after oral gavage and intravenous administration of BLA at a single dose of 0.04, 0.12, 0.36 mg/kg (oral) or 0.02 mg/kg (i.v.) in male Sprague-Dawley rats. Plasma concentration profiles were analysed using a non-compartmental pharmacokinetic method. Following i.v. 0.02 mg/kg and oral administration 0.04, 0.12 or 0.36 mg/kg, the geometric mean Cmax values were 19.97, 2.11, 5.11 and 11.47 ng/ml, respectively; the corresponding geometric mean AUC(0-t) values were 10.50, 3.19, 9.59 and 18.10 ng x h/ml, respectively. The median Tmax values were 0.033, 0.167, 0.167 and 0.167 h, respectively. The terminal elimination half-lives (t1/2) were 1.23, 2.48, 1.93 and 2.17h, respectively. The results showed that Cmax and AUC(0-t) increased with increasing doses of BLA. The increase in exposure with increasing dose was lower than expected under conditions of strict proportionality.