The pharmacokinetics and conversion of the lactone to the carboxylate forms of ginkgolide B in rat plasma
The pharmacokinetics and conversion of the lactone to the carboxylate forms of ginkgolide B in rat plasma
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DOI：
10.1080/10286020.2013.764866
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发表时间：
2013-04
影响因子：
1.7
通讯作者：
Dian-lei Wang;D. Peng;Xiu-hua Tao;Yin Cao;Wei-dong Chen;Yan Liang;Lin Xie;Xiao-dong Liu
中科院分区：
文献类型：
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作者：
Dian-lei Wang;D. Peng;Xiu-hua Tao;Yin Cao;Wei-dong Chen;Yan Liang;Lin Xie;Xiao-dong Liu
银杏内酯B由三个内酯基团组成，在不同pH值的水溶液中可发生水解并导致开环。从体内药理活性机制来看，内酯似乎是药物的活性形式。静脉注射4 mg/kg银杏内酯B后，研究了银杏内酯B的内酯型（GB-lac）以及内酯型和羧酸酯型总量（GB-tot）的药代动力学。还研究了体外血浆中内酯水解率。静脉注射后，原始形式的银杏内酯B在模拟生理条件下转化为羧酸盐形式。 GB-lac 的 AUC0 − ∞ 占 GB-tot 的 AUC0 − ∞ 的 63.5 ± 17.4%。尿液中内酯与羧酸盐的平均累积排泄比例达到约1:1。从体外大鼠血浆中内酯水解的平衡来看，k obs 为− 0.0176 min− 1，t 1/2 为39.38 min。综上所述，在生理pH值下，体内银杏内酯B的内酯与其羧酸盐之间存在平衡，这表明应更多地关注银杏内酯B的原始形式和电离形式以及内酯在体内向羧酸盐的转化。
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.