title: Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography-tandem mass spectrometry.
abstract: BACKGROUND
  Fritillaria thunbergii Miq. has been traditionally used in China as antitussive and expectorant herbs, and newly used in the clinical treatment of leukemia in recent years.
  
  
  OBJECTIVE
  To investigate whether gender exerted a significant influence on the pharmacokinetics, tissue distribution and excretion of peimine and peiminine in Sprague-Dawley rats who were given a single oral administration of 4.25 g/kg Fritillaria thunbergii Miq. extract.
  
  
  METHODS
  Sprague-Dawley rats were assigned into two groups based on the gender and orally administered 4.25 g/kg Fritillaria thunbergii Miq. extract for each individual pharmacokinetics, tissue distribution and excretion study.
  
  
  RESULTS
  Compared with female rats, peimine and peiminine were eliminated slowly from male rat plasma, and significant gender-related differences were observed in the pharmacokinetic parameters. Drug blood and tissue levels in male rats were significantly higher than the female counterparts except for several tissues, such as fat, muscle and skin. Gender also exerted a significant influence on the urine excretion but such effect was not observed in the feces excretion study.
  
  
  CONCLUSIONS
  Gender exerted a significant influence on the pharmacokinetics, tissue distribution and urine excretion of peimine and peiminine. It is assumed that the sex-associated differences of peimine and peiminine in rats might be mainly result from sex-dependent expression and activity of drug metabolism enzymes and P-glycoprotein.
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of TCM, No.18 Yun Wan Road, Nanchang 330004, PR China. chlly98@163.com
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Zhang
authors.forename: Zhi-yu
authors.initials: ZY
authors.lastname: Guan
authors.forename: Wei-feng
authors.initials: WF
authors.lastname: Zhu
authors.forename: Wen-jiao
authors.initials: WJ
authors.lastname: Yi
authors.forename: Yong-mei
authors.initials: YM
authors.lastname: Guan
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Hong-ning
authors.initials: HN
authors.lastname: Liu
mesh_terms: D000818:Animals; D002595:Cevanes / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D031410:Fritillaria / Q000737:chemistry; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D002595:Cevanes; D010936:Plant Extracts; C014242:verticine; C047331:peiminine