Pharmacokinetics of cerivastatin when administered under fasted and fed conditions in the morning or evening

Objective: The influence of food and time of drug dosing on the pharmacokin etics of cerivastatin, a potent HMG-CoA reductase inhibitor, was evaluated in 24 healthy male subjects between 21 and 44 years of age. Methods: A sing le-dose, four-way crossover design was employed, with each subject receivin g cerivastatin 0.8 mg at weekly intervals under each of four conditions: 8 a.m. dosing after an overnight fast (reference), 8 a.m. dosing with a high- fat breakfast (test), 6 p.m. dosing with the evening meal (low-fat; test), and 10 p.m. dosing 4 h after dinner (reference). Plasma concentrations of t he parent compound and its active metabolites were measured by high perform ance liquid chromatography with fluorescence detection subsequent to post-c olumn derivatization. Results: The calculated 90% confidence intervals for cerivastatin AUC and C-max were completely contained within the range 0.8 t o 1.25. Thus, no relevant influence of food could be detected, although the presence of food increased the C-max of cerivastatin on average by 12% (90 % confidence interval: 1.04 - 1.21) under morning, but not evening dosing. With respect to the effect of daytime on cerivastatin pharmacokinetics, AUC s were bioequivalent for all treatment conditions, with C-max values slight ly lower (8 - 19%) following evening dosing, irrespective of food intake. C erivastatin was well tolerated by the subjects in the study. Conclusion: Fo od effect bioequivalence according to current guidelines could be demonstra ted. Cerivastatin can be administered independent of meal intake at dinner or at bedtime, the preferred time of dosing for statins because the rate of hepatic cholesterol synthesis is greatest at night.