PHARMACODYNAMIC EFFECTS AND PHARMACOKINETICS OF ATORVASTATIN AFTER ADMINISTRATION TO NORMOCHOLESTEROLEMIC SUBJECTS IN THE MORNING AND EVENING

The phormacodynamic effects and pharmacokinetics of atorvastatin, a po tent investigational inhibitor of HMG-CoA reductase, were studied in 1 6 normolipidemic subjects after administration of 40 mg daily for 25 d ays in the morning or evening. Lipid and apolipoprotein parameters wer e determined, and plasma atorvastatin equivalent concentrations were m easured according to a validated enzyme inhibition bioassay procedure. Atorvastatin was well tolerated by the participants. Overall, mean re ductions of 34% in total cholesterol, 48% in low-density lipoprotein ( LDL) cholesterol, 37% in very low density lipoprotein (VLDL) cholester ol, 25% in triglycerides, 6% in apolipoprotein A-I, and 34% in apolipo protein B were observed. Changes in lipid and apolipoprotein values we re similar after morning and evening administration of atorvastatin. I n contrast, studies with other HMG-CoA reductase inhibitors have consi stently shown that evening administration results in larger reductions in total and LDL cholesterol than does morning administration. Rate a nd extent of equivalent absorption of atorvastatin were lower during e vening than morning administration. Mean elimination half-life values were similar, however, suggesting that there is no diurnal variation i n disposition of this drug. Pharmacokinetic differences did not correl ate with effects on serum lipids.