Pharmacokinetics, tissue distribution, excretion, and metabolism of a new cardioprotective agent 10-O-dimethylaminoethylginkgolide B in rats

Abstract

The plasma pharmacokinetics, tissue distribution, excretion, and metabolism of 10-O-dimethylaminoethylginkgolide B (XQ-1H), a protective agent against cardiovascular accident for its potential anti-platelet-activating factor activity, were investigated in rats. Plasma profiles were obtained after intravenous administration of 4, 8, 16, and 32 mg/kg of XQ-1H. There was a gender difference in the pharmacokinetics of XQ-1H. The elimination half-life of XQ-1H was 209.55, 200.81, 236.95, and 269.78 min in female rats and was 139.63, 173.83, 191.28, and 228.0 min in male rats at doses of 4, 8, 16, and 32 mg/kg, respectively. At four dose levels, female rats have higher values for area under the curve (AUC) than male rats. XQ-1H had linear pharmacokinetic characteristics in rats within the dose ranges tested. The volume of distribution in rats ranged from 6.05 to 15.09 l/kg. XQ-1H showed an extensive distribution into multiple tissues and reached its maximal concentration in all tissues at 10 min post-dose. About 80% of XQ-1H was mainly converted to its hydrolyzed and demethylated metabolites in vivo, and the elimination of unchanged compound was minor ( < 20%) in rats.

Keywords:

• 10-O-dimethylaminoethylginkgolide B
• pharmacokinetics
• tissue distribution
• excretion
• metabolism

Acknowledgements

This study was financially supported by National Natural Science Foundation of China (No. 81001592), the Key Project of Chinese Ministry of Education (No. 210101), and the Key Project of Anhui University Provincial Natural Science Research Foundation (No. KJ2010A210).