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Atorvastatin is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that reduces plasma cholesterol by inhibiting cholesterol synthesis and increasing cellular uptake of low density lipoproteins. The effects of age and gender on the pharmacokinetics of atorvastatin after administration of single 20-mg tablets of atorvastatin were studied in 16 young and 16 elderly volunteers (8 men and 8 women in each age group). Plasma equivalent concentrations of atorvastatin were quantitated by a validated enzyme inhibition bioassay. Atorvastatin was well tolerated by the participants. The equivalent maximum concentration (Cmax) of atorvastatin was 42.5% higher in elderly participants (age, 66-92 years) than in young participants (age, 19-35 years) and 17.6% higher in women than in men. In addition, mean area under the concentration-time curve (AUC0-∞) and half-life (t½) 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 women than in men. Because the primary site of action for HMG-CoA reductase inhibitors is the liver and atorvastatin is subject to extensive first-pass hepatic metabolism, it is unclear whether these age- and gender-related differences in the pharmacokinetics of atorvastatin will be clinically important. Results of subsequent safety and efficacy trials should help clarify the clinical significance of these pharmacokinetic differences.