title: Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens Thunb extract in rats.
abstract: BACKGROUND
  Ajuga decumbens Thunb is a medicinal plant native to China popularly used to treat chronic pelvic inflammation and hysteromyoma. Its main bioactive components are iridoid glycosides, such as 8-O-acetylharpagide and harpagide that had presented antibacterial, anti-inflammatory, and antiviral activities.
  
  
  OBJECTIVE
  To establish a sensitive LC-MS/MS method and compare the pharmacokinetics of 8-O-acetylharpagide and harpagide in rats after oral administration of their pure forms and from compounds obtained from Ajuga decumbens extract.
  
  
  METHODS
  Rats received orally 15 mg/kg (equivalent of 6 mg/kg 8-O-acetylharpagide and 1.5mg/kg harpagide), 30 mg/kg and 60 mg/kg of Ajuga decumbens Thunb extract and were compared to animals that received 12 mg/kg of 8-O-acetylharpagide or 3mg/kg of harpagide p.o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartmental analysis.
  
  
  RESULTS
  Results showed that the iridoid glycosides were quickly absorbed by oral route and showed a dose-dependence profile. Pharmacokinetic parameters of both glycosides were essentially the same except Tmax when dosed as the extract or pure forms.
  
  
  CONCLUSIONS
  8-O-acetylharpagide was metabolized to harpagide, which affected the pharmacokinetic profiles of harpagide when dosed as the extract. This pharmacokinetic study seems to be useful for a further clinical study of Ajuga decumbens Thunb extract.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, PR China.
authors.forename: Binyu
authors.initials: B
authors.lastname: Wen
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Pengyue
authors.initials: P
authors.lastname: Li
authors.forename: Qihua
authors.initials: Q
authors.lastname: Xu
authors.forename: Yanli
authors.initials: Y
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Jianrong
authors.initials: J
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D031328:Ajuga; D000818:Animals; D004347:Drug Interactions; D057889:Iridoid Glycosides / Q000097:blood / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000494:pharmacology*; D011714:Pyrans / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D057889:Iridoid Glycosides; D010936:Plant Extracts; D011714:Pyrans; C077626:8-O-acetylharpagide; C033250:harpagide