A Study of the Pharmacokinetics and Bioavailability of Sustained-release Lovastatin Capsules in Dogs

Objective To study the pharmacokinetics and relative bioavailability of sustained-release lovastatin capsules in healthy Beagle dogs and to assess the bioequivalence and performance of the sustained release of the capsules. Methods Following a single dose of 40 mg of the sustained-release lovastatin capsules(test preparation) and conventional lovostatin capsules(reference preparation) administered by gastrogavage to each of the 4 dogs in a randomized crossover design,the plasma levels of the active drugs at different time points thereafter were determined with HPLC and the plasma drug concentration-time curves of these preparations were drawn.The pharmacokinetic parameters as well as the relative bioavailability were calculated. Results The Tmax values of the test preparation and reference preparation were(2.167±0.408) and((3.167)±0.408)h;the C_(max) values were(23.960±6.091) and(14.307±4.319) nmol·L~(-1);and the AUC_(0~t) were(118.647±13.369) and(129.065±14.729) nmol·h·L~(1),respectively.Calculated with AUC and compared with the reference preparation,the relative bioavailability of lovastatin in the test preparation was (110.4±9.6)% in average.The results of variance analysis showed that the differences between the test and reference preparations with respect to periods and preparations were not significant(P0.05).The differences between individual subjects,however,were significant.The 90% confidence interval of AUC_(0~t) of the test praparation was 101.3%～119.5% of that of the reference preparation. Conclusion The sustained-release lovastatin capsules and the conventional lovastatin capsules were shown to be bioequivalent in terms of the degree of absorption.