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 pharmacokinetics of cerivastatin, a potent HMG-CoA reductase inhibitor, was evaluated in 24 healthy male subjects between 21 and 44 years of age.


METHODS
A single-dose, four-way crossover design was employed, with each subject receiving 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 the parent compound and its active metabolites were measured by high performance liquid chromatography with fluorescence detection subsequent to post-column derivatization.


RESULTS
The calculated 90% confidence intervals for cerivastatin AUC and Cmax were completely contained within the range 0.8 to 1.25. Thus, no relevant influence of food could be detected, although the presence of food increased the Cmax 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, AUCs were bioequivalent for all treatment conditions, with Cmax values slightly lower (8 - 19%) following evening dosing, irrespective of food intake. Cerivastatin was well tolerated by the subjects in the study.


CONCLUSIONS
Food effect bioequivalence according to current guidelines could be demonstrated. 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.
Mück
W
W
Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany.
Frey
R
R
Unger
S
S
Voith
B
B
D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D005215:Fasting; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin