CIMETIDINE DOES NOT ALTER ATORVASTATIN PHARMACOKINETICS OR LDL-CHOLESTEROL REDUCTION

Objective: To determine the effects of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxymeth ylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Methods: Twelve h ealthy subjects participated in a randomized two-way crossover study. Each subject received atorvastatin 10 mg every morning for 2 weeks and atorvastatin 10 mg every morning with cimetidine 300 mg four times a day for 2 weeks, separated by a 4-week washout period. Steady-state ph armacokinetic parameters (based on an enzyme inhibition assay) and lip id responses were compared. Results: Pharmacokinetic parameters and li pid responses were similar following administration of atorvastatin al one and atorvastatin with cimetidine. Mean values for C-max (the maxim um concentration) were 5.11 ng.eq.ml(-1) and 4.54 ng.eq.ml(-1), for t( max) (the time to reach maximum concentration) 2.2 h and 1.3 h, for AU C(0-24) (area under the concentration-time curve from time 0 h to 24 h ) 58.6 ng.eq.h ml(-1) and 58.5 ng.eq.h ml(-1), and for t(1/2) (termina l half-life) 10.1 h and 17.0 h, respectively, following administration of atorvastatin alone and atorvastatin with cimetidine. Following tre atment with atorvastatin alone and atorvastatin with cimetidine, mean values for the percentage change from baseline for total cholesterol w ere -29.5% and -29.9%, for low-density lipoprotein (LDL) cholesterol - 41.0% and -42.6%, for high-density lipoprotein (HDL) cholesterol 6.3% and 5.8%, and for triglycerides -33.8% and -25.8%, respectively. Concl usions: The rate and extent of atorvastatin absorption and the effects of atorvastatin on LDL-cholesterol responses are not influenced by co administration of cimetidine.