title: Pharmacokinetic interaction between febuxostat and morin in rats.
abstract: BACKGROUND
  Due to wide consumption of flavonoids in the dietary supplement, and an imperative role of CYPs and P-glycoprotein inhibition in drug disposition. So there is increasing scientific interest in drug-flavonoid interactions.
  
  
  OBJECTIVE
  The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of febuxostat in rats.
  
  
  METHODS
  A simple ultra-performance liquid chromatography method has been developed for the calculation of febuxostat in 100 µl rat plasma using febuxostat D7 as an internal standard (IS). The assay procedure involved a single-step, liquid-liquid extraction of febuxostat and IS from plasma with methanol. Pharmacokinetic parameters of febuxostat were determined in rats after an oral administration of febuxostat (5 mg/kg) to rats in the control, coadministered and pretreated groups of morin (10 mg/kg).
  
  
  RESULTS
  Compared to the control rats given febuxostat alone, the Cmax and AUC of febuxostat increased by 18 - 20 and 47 - 50%, respectively, in rats pretreated with morin. The plasma half-life (t1/2) of the pretreated group is increased by 2.5-fold compared with the control group. Consequently, relative bioavailability values of febuxostat in the rats pretreated with morin were significantly higher (p < 0.05) than those from the control and coadministered groups. Increased bioavailability indicates that the presence of morin could be effective in inhibiting CYP1A1, CYP1A2 and CYP3A4-mediated metabolism and/or effective in inhibiting P-glycoprotein-mediated cellular efflux of febuxostat.
  
  
  CONCLUSIONS
  The presence of morin significantly enhanced the oral exposure of febuxostat, suggesting that concurrent use of morin or morin-containing dietary supplements with febuxostat should be verified to avoid drug-flavonoid interactions.
authors: Jamia Hamdard University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry , Hamdard Nagar, New Delhi 110062 , India +91 11 2605 9688 5650 ; +91 11 2704 8685 prof.anees1@gmail.com.
authors: Kapendra
authors: K
authors: Sahu
authors: Anees A
authors: AA
authors: Siddiqui
authors: Mohammad
authors: M
authors: Shaharyar
authors: Sachin
authors: S
authors: Malik
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000069465:Febuxostat; D005419:Flavonoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D047309:Flavones
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000069465:Febuxostat; D005419:Flavonoids; D013844:Thiazoles; C008548:morin; D047309:Flavones