Stereoselective pharmacokinetics of flobufen in rats

✍ Scribed by Frantisek Trejtnar; Vladimir Wsol; Barbora Szotakova; Lenka Skalova; Petr Pavek; Miroslav Kuchar

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 101 KB
• Volume: 11
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1999)11:10<781::aid-chir7>3.0.co;2-9

✦ Synopsis

Stereoselectivity of the pharmacokinetics of the nonsteroidal antiinflammatory drug flobufen, 4-(2Ј,4Ј-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid, was studied in male Wistar rats after intravenous administration. Pharmacokinetic parameters and chiral inversion of flobufen enantiomers were studied after a bolus injection of the racemate and individual enantiomers (5 mg/kg). Determinations of the enantiomers in rat plasma were performed using chiral HPLC (terguride column). After i.v. administration of flobufen racemate, plasma levels of R-enantiomer decreased more rapidly. The S-/R-enantiomer ratio of AUCs after rac-flobufen was 13.3. The total plasma clearance value of S-flobufen was more than 10-fold lower than R-flobufen. The other pharmacokinetic parameters of the enantiomers were also significantly different. While only traces of R-enantiomer (less than 1%) were detected in rat plasma after S-flobufen administration, considerable conversion to the S-enantiomer was found after injection of R-flobufen (R-enantiomer AUC/S-enantiomer AUC = 0.52). The results indicate substantial stereoselectivity in the disposition of flobufen enantiomers in the rat, which is, at least in part, attributed to chiral bioconversion. Chirality 11: 781-786, 1999.