Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening

The pharmacodynamic effects and pharmacokinetics of atorvastatin, a potent investigational inhibitor of HMG-CoA reductase, were studied in 16 normolipidemic subjects after administration of 40 mg daily for 15 days in the morning or evening. Lipid and apolipoprotein parameters were determined, and plasma atorvastatin equivalent concentrations were measured according to a validated enzyme inhibition bioassay procedure. Atorvastatin was well tolerated by the participants. Overall, mean reductions of 34% in total cholesterol, 48% in low-density lipoprotein (LDL) cholesterol, 37% in very low density lipoprotein (VLDL) cholesterol, 25% in triglycerides, 6% in apolipoprotein A-I, and 34% in apolipoprotein B were observed. Changes in lipid and apolipoprotein values were similar after morning and evening administration of atorvastatin. In contrast, studies with other HMG-CoA reductase inhibitors have consistently shown that evening administration results in larger reductions in total and LDL cholesterol than does morning administration. Rate and extent of equivalent absorption of atorvastatin were lower during evening than morning administration. Mean elimination half-life values were similar, however, suggesting that there is no diurnal variation in disposition of this drug. Pharmacokinetic differences did not correlate with effects on serum lipids.
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