Population pharmacokinetics of atorvastatin, simvastatin and pravastatin after oral administration in humans

The purpose of this study is to determine the population pharmacokinetics of 3 statins after oral dosing. This was achieved by simultaneous data fitting of 101 different individuals from three studies: 25 subjects for pravastatin, 40 subjects for simvastatin and 36 subjects for atorvastatin. Each study was fitted separately. Plasma profiles were best characterized by 1 -compartment model for pravastatin, 2-compartment model for simvastatin, and 3 -compartment model for atorvastatin. The criteria used for model building involved the examination of the fitted cuves, the improvement in objective function and statistical tests: Akaike test, Schwarz test and log likelihood test; and examining the improvement in residual plots. The elimination rate constant and clearance values for pravastatin is higher than simvastatin and higher than atorvastatin which is in agreement with models used. The variability, as indicated by population coefficient of variation, is generally higher than 30% rendering them highly variable drugs

Pharmacokinetic behavior of two tablet formulations of mefenamic acid in healthy volunteers

The pharmacokinetic behavior of single dose of two mefenamic acid tablet formulations was studied in a randomized cross over design in 19 healthy male volunteers. The two products [Fendol DS and Ponstan Forte] were found similar in weight and content uniformity, however Fendol DS tablets had a faster dissolution rate compared to Ponstan Forte. Following ingestion of 500 mg of either of the products blood samples were obtained over a 14 h period and the serum drug concentrations were determined by an HPL assay with ultraviolet detection at 280 nm. The parametric 90% confidence intervals of the mean value of the ratio [Fendol DS/Ponstan Forte] of Pharmacokinetic parameters were 0.91-1.15, 0.92-1.13,0.92-1.23, and 0.94-1.15 for AUC [0'14h], AUC[0-infinity], C[max] and T[1/2], respectively. In each case values were within the acceptable bioequivalence range of 0.8-1.25. Point estimate of the difference of T [max] between the two formulations [Fendol DS - Ponstan Forte] was 0.16 hours with a 90% confidence interval of -0.33-0.64 which overlaps with the stipulated bioequivalence range of +/- 0.39. The kinetic parameters are comparable to what is reported for mefenamic acid and there were no statistically significant differences in any of them when comparing the two products. Thus, the two products could be considered bioequivalent regarding rate of absorption C [max] and T [max], extent of absorption [C[max] and AUC] and elimination t [1/2]