title: 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.
authors.affiliation: Key Laboratory of Modernized Chinese Materia and Laboratory of Drug Metabolism and Pharmacokinetics, Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors.forename: Dian-Lei
authors.initials: DL
authors.lastname: Wang
authors.forename: Dai-Yin
authors.initials: DY
authors.lastname: Peng
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Xin-Ting
authors.initials: XT
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D001826:Body Fluids / Q000378:metabolism; D002316:Cardiotonic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D046934:Ginkgolides / Q000737:chemistry / Q000493:pharmacokinetics*; D007783:Lactones / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C570654:10-O-dimethylaminoethylginkgolide B; D002316:Cardiotonic Agents; D046934:Ginkgolides; D007783:Lactones