Pharmacokinetic and bioequivalence studies of fast dispersible ketoprofen tablets in healthy volunteers

Abstract

In the present study the pharmacokinetic and bioequivalence parameter of Ketoprofen 100 mg fast dispersible tablets (test) were measured with marketed (reference) product. This study was accomplished following FDA guidance. A single dose, open labeled, cross over (two way), randomized study design was used to conduct investigation on 12 Pakistani healthy volunteers. At various time points blood samples (10mL) were drawn i.e. at 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 13hr. Plasma was then separated and ketoprofen concentrations were estimated by validated HPLC technique using LC 20A pump (Shimadzu Corp, Japan) and Spectrophotometric SPD-20Adetector (Shimadzu Corp, Japan). Ketoprofen concentrations were then analyzed by KineticaTM 4.4.1 (Thermo electron corp, USA) to estimate various compartmental and noncompartmental pharmacokinetic parameters. Various parameters of bioequivalence including AUCtot, AUC0-∞, AUClast, Tmaxcalc and Cmaxcalcw ere compared using ANOVA method (two way). For log and non-log transformed data the 90 % confidence interval values for AUC0-∞ (1.0087-1.0704; 1.0099-1.0714), AUCtot (0.95482- 1.0093; 0.95486-1.0098), AUClast (0.93373-0.98605; 0.93404-0.98603), Cmaxcalc (0.92978-0.9955; 0.92962-0.99663) and Tmaxcalc (0.89019-0.94116; 0.89095-0.94288) for test and reference products respectively. Results were found to be within the FDA satisfactory range. For the results verification, Schuirman’s one sided t test was used. SPSS 17.0 (SPSS Inc) was utilized for the determination of wilcoxon sign rank test. Results showed no carry over effect after first study period. Also test product met the regulatory criteria for bioequivalence with the reference product. Both the formulations were well tolerated.