title: Dose-dependent pharmacokinetics of bulleyaconitine A in rats.
abstract: 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.
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: H R
authors.initials: HR
authors.lastname: Xu
authors.forename: G X
authors.initials: GX
authors.lastname: Ji
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: X N
authors.initials: XN
authors.lastname: Li
authors.forename: Y J
authors.initials: YJ
authors.lastname: Gong
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Shen
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D000700:Analgesics; C052509:bulleyaconitine A; D000157:Aconitine