title: The pharmacokinetics and bioavailability of three canthinone alkaloids after administration of Kumu injection to rats.
abstract: BACKGROUND
  Kumu injection (KMI) is made from the branches and stems of Picrasma quassiodes (D. Don) Benn. and has been used clinically for the treatment of upper respiratory tract infection, acute tonsillitis, enteritis and bacillary dysentery. 3-methylcanthin-2,6-dione, 5-hydroxy-4-methoxycanthin-6-one, 4,5-dimethoxycanthin-6-one are the active ingredients of KMI because of its therapeutic effects.
  
  
  OBJECTIVE
  To develop a LC-MS/MS method for simultaneous determination of three active canthinone alkaloids (4,5-dimethoxycanthin-6-one, 5-hydroxy-4-methoxycanthin-6-one and 3-methylcanthin-2,6-dione) in rat plasma and for the pharmacokinetic study of them after administered of KMI to rats.
  
  
  METHODS
  Rats were divided into 5 groups (n=5 per group), 3 groups administered intramuscularly with a single dose of KMI at 0.30, 0.45 and 0.90mL/kg respectively, and the other 2 groups administered intragastically or intravenously a single dose of KMI at 0.9mL/kg respectively. The concentrations of 4,5-dimethoxycanthin-6-one, 5-hydroxy-4-methoxycanthin-6-one and 3-methylcanthin-2,6-dione in plasma were determined by the established LC-MS/MS method at different time points and the pharmacokinetic parameters were estimated by non-compartmental analysis.
  
  
  RESULTS
  Pharmacokinetic results indicated that all of the alkaloids were absorbed rapidly and 3-methylcanthin-2,6-dione was eliminated fastest in rats. After intramuscular administration of KMI to rats, the absolute bioavailability is excellent, and the pharmacokinetic profiles are characterized by the first order kinetics.
  
  
  CONCLUSIONS
  The established method is suitable for the quantitation of the three alkaloids in rat plasma. And this pharmacokinetic study suggested that intramuscular injection of KMI was suitable in clinical usage.
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Miao
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China. Electronic address: wj-queen@163.com.
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China. Electronic address: cy101610@qq.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000470:Alkaloids / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002243:Carbolines / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D007273:Injections, Intramuscular; D008297:Male; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D000470:Alkaloids; D002243:Carbolines
keywords: Bioavailability; Canthinone alkaloids; Kumu injection; LC-MS/MS; Pharmacokinetics; Rat plasma