Objective: To determine the effects of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor.
Methods: Twelve healthy 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 pharmacokinetic parameters (based on an enzyme inhibition assay) and lipid responses were compared.
Results: Pharmacokinetic parameters and lipid responses were similar following administration of atorvastatin alone and atorvastatin with cimetidine. Mean values for Cmax (the maximum concentration) were 5.11 ng eq.ml(-1) and 4.54 ng eq.ml(-1), for tmax (the time to reach maximum concentration) 2.2 h and 1.3 h, for AUC0-24 (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 t1/2 (terminal half-life) 10.1 h and 17.0 h, respectively, following administration of atorvastatin alone and atorvastatin with cimetidine. Following treatment with atorvastatin alone and atorvastatin with cimetidine, mean values for the percentage change from baseline for total cholesterol were -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.
Conclusions: The rate and extent of atorvastatin absorption and the effects of atorvastatin on LDL-cholesterol responses are not influenced by coadministration of cimetidine.