title: Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss.
abstract: BACKGROUND
  Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents.
  
  
  METHODS
  A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined.
  
  
  RESULTS
  The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Pharmacokinetics of xanthomicrol in rats.
authors.affiliation: Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Seyedeh-Somayeh
authors.initials: SS
authors.lastname: Zamani
authors.affiliation: Department of Pharmaology, School of Medicine, Tehran University for Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Hossieni
authors.affiliation: Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Etebari
authors.affiliation: Sarem Fertility and Infertility Research Centre, Sarem Hospital, P.O. Box 1396956111, Shahrak-e-Ekbatan, Tehran, Iran.
authors.forename: Pirooz
authors.initials: P
authors.lastname: Salehian
authors.affiliation: Department of Pharmacology, Iran University for Medical Sciences, Tehran, Iran. ebrahimi.sa@iums.ac.ir.
authors.forename: Soltan Ahmad
authors.initials: SA
authors.lastname: Ebrahimi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D047309:Flavones / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D019686:Lamiaceae; D008099:Liver / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D020533:Angiogenesis Inhibitors; D047309:Flavones; D010936:Plant Extracts; C462036:xanthomicrol; C533734:calycopterin; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Calycopterin; Dracocephalum kotschyi; Flavonoids; Pharmacokinetics; Xanthomicrol