title: Pharmacokinetics, Metabolism and Disposition of [14C]XQ-1H After Intravenous Administration to Male Rats.
abstract: This study describes the in vivo pharmacokinetics and metabolism of [14C]labeled XQ-1H in male rats.
  
  
  
  XQ-1H is a methanesulfonate of XQ, 10-O-(N,N-dimethylaminoethyl)-ginkgolide B, a derivative of ginkgolide B (GB) with enhanced water solubility. Since it is very difficult to synthesize radiolabeled GB, the results obtained in this study may provide helpful insight to further ADME investigation of GB and its analogue compounds. After an i.v. administration of [14C]XQ-1H to male rats, XQ (the freebase form of XQ-1H) was extensively hydrolyzed, moderately metabolized, and mainly excreted in feces (71.5% of the dose) via the biliary route.
  
  
  
  The main enzyme mediated metabolic pathways were mono- and di-demthylation. Using the radiolabel form of XQ-1H, the temporal binding of XQ to red blood cells was observed.
  
  
  
  Binding of XQ to RBCs may lower the blood's viscosity and thus provide symptomatic improvement of ischemic stroke patients.
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Technology University, Nanjing 210009, Jiangsu. China.
authors.forename: Yinlin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Jiangsu Carephar Pharmaceutical Co., Ltd, Nanjing 210014, Jiangsu. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Jiangsu Carephar Pharmaceutical Co., Ltd, Nanjing 210014, Jiangsu. China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Jin
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Technology University, Nanjing 210009, Jiangsu. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Guo
authors.affiliation: XBLChina, Inc., a Subsidiary of LTD, WuXi AppTec, Nanjing, Jiangsu 210038. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: XenoBiotic Laboratories, Inc., a Subsidiary of LTD, WuXi AppTec, Plainsboro, New Jersey, 08536. China.
authors.forename: Dennis
authors.initials: D
authors.lastname: Heller
authors.affiliation: XBLChina, Inc., a Subsidiary of LTD, WuXi AppTec, Nanjing, Jiangsu 210038. China.
authors.forename: Zhe-Ming
authors.initials: ZM
authors.lastname: Gu
mesh_terms: D000818:Animals; D001809:Blood Viscosity / Q000187:drug effects*; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy*; D002250:Carbon Radioisotopes / Q000737:chemistry; D000073398:Demethylation; D004912:Erythrocytes / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D020441:Ginkgo biloba / Q000737:chemistry; D046934:Ginkgolides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D065669:Hepatobiliary Elimination; D007275:Injections, Intravenous; D007783:Lactones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D046934:Ginkgolides; D007783:Lactones; C544311:XQ-1H compound; C000615234:Carbon-14
keywords: PAF
  antagonist; [14C]XQ-1H; ginkgolide B derivative; high resolution LC-MS; ischemic stroke; mass balance; metabolism; radiolabeling technology