title: The pharmacokinetics and conversion of the lactone to the carboxylate forms of ginkgolide B in rat plasma.
abstract: Ginkgolide B consists of three lactone groups, which may undergo hydrolysis, and lead to the rings opening in aqueous solution with different pHs. From mechanisms of pharmacological activity in vivo, the lactone appears to be the active form of the drug. Pharmacokinetics of lactone form (GB-lac) and the total of the lactone and carboxylate form (GB-tot) of ginkgolide B were investigated after intravenous administration of a dose of 4 mg/kg ginkgolide B. The rate of lactone hydrolysis was also studied in plasma in vitro. After intravenous administration, ginkgolide B in the original form was converted to its carboxylate form under simulated physiological conditions. The AUC0 - ∞ of GB-lac constituted 63.5 ± 17.4% of the AUC0 - ∞ of GB-tot. The ratio of average cumulation of excretion of lactone to carboxylate reached approximately 1 to 1 in urine. From the equilibrium of lactone hydrolysis in rat plasma in vitro, the k obs was - 0.0176 min(- 1) and t 1/2 was 39.38 min. In conclusion, the equilibrium existed between lactone of ginkgolide B and its carboxylate form in vivo at physiological pH, which suggested that more attention should be focused on the original and the ionization forms of ginkgolide B and the conversion of the lactone into carboxylate in vivo.
authors: Key Laboratory of Modernized Chinese Materia, Laboratory of Drug Metabolism and Pharmacokinetics, Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors: Dian-Lei
authors: DL
authors: Wang
authors: Dai-Yin
authors: DY
authors: Peng
authors: Xiu-Hua
authors: XH
authors: Tao
authors: Yin
authors: Y
authors: Cao
authors: Wei-Dong
authors: WD
authors: Chen
authors: Yan
authors: Y
authors: Liang
authors: Lin
authors: L
authors: Xie
authors: Xiao-Dong
authors: XD
authors: Liu
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007783:Lactones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002264:Carboxylic Acids; D046934:Ginkgolides; D007783:Lactones; C045856:ginkgolide B