EFFECT OF AGE AND GENDER ON PHARMACOKINETICS OF ATORVASTATIN IN HUMANS

Atorvastatin is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that reduces plasma cholesterol by inhibiting chol esterol synthesis and increasing cellular uptake of low density lipopr oteins. The effects of age and gender on the pharmacokinetics of atorv astatin after administration of single 20-mg tablets of atorvastatin w ere studied in 16 young and 16 elderly volunteers (8 men and 8 women i n each age group). Plasma equivalent concentrations of atorvastatin we re quantitated by a validated enzyme inhibition bioassay. Atorvastatin was well tolerated by the participants. The equivalent maximum concen tration (C-max) of atorvastatin was 42.5% higher in elderly participan ts (age, 66-92 pears) than in young participants (age, 19-35 years) an d 17.6% higher in women than in men. In addition, mean area under the concentration-time curve (AUC(0-infinity)) and half-life (t(1/2)) were 27.3% greater and 36.2% longer, respectively, in elderly adults than in young adults and 11.3% lower and 19.9% shorter, respectively, in wo men than in men. Because the primary site of action for HMG-CoA reduct ase inhibitors is the liver and atorvastatin is subject to extensive f irst-pass hepatic metabolism, it is unclear whether these age- and gen der-related differences in the pharmacokinetics of atorvastatin will b e clinically important. Results of subsequent safety and efficacy tria ls should help clarify the clinical significance of these pharmacokine tic differences.