Abstract
Interstrain differences in the pharmacokinetic behaviour of drugs can influence their plasma concentration-time profiles and the extent of drug exposure, thereby influencing the outcome of animal toxicity studies. The pharmacokinetics of flurbiprofen was investigated in Wistar and Sprague–Dawley rats, the two most commonly used strains in toxicity studies. Flurbiprofen was administered orally at a dose of 2 mg kg−1 in a solution of polyethylene glycol) 400, to male and female Wistar and Sprague–Dawley rats. Serial blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12h postdose by jugular vein cannulation. Wistar rats exhibited significantly higher peak plasma concentrations with a significant decrease in Vd/F. Within each strain, animals of each sex had similar absorption and distribution kinetics. However, male rats in both strains exhibited faster elimination and clearance, with a corresponding decrease in AUC0-∞. These differences were significant only in the Wistar strain. The results confirm the occurrence of significant interstrain and sex differences in the disposition of flurbiprofen in Wistar and Sprague–Dawley rats.
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