THE PHARMACOKINETICS AND PHARMACODYNAMICS OF NIFEDIPINE AT STEADY-STATE DURING CONCOMITANT ADMINISTRATION OF CIMETIDINE OR HIGH-DOSE RANITIDINE

Ranitidine may be used at doses of up to 300 mg twice daily in the healing of duodenal ulcers, and this study investigated the potential for a pharmacokinetic or pharmacodynamic interaction between nifedipine 10 mg three times daily and ranitidine 300 mg twice daily compared with cimetidine 800 mg daily and placebo in a randomised crossover study in 18 healthy male subjects. Twelve blood samples were taken on the fifth day in each treatment period and assayed for nifedipine by h.p.l.c. Pulse, blood pressure and ECG recordings were also taken. Cimetidine, but not ranitidine, produced significant changes in the pharmacokinetics of nifedipine at steady state. Mean +/- s.d. values of AUC were 105 +/- 40-mu-g l-1 h for placebo treatment, 111 +/- 45-mu-g l-1 for ranitidine and 211 +/- 64-mu-g l-1 h for cimetidine (P < 0.001), and C(max) values were 33 +/- 14, 39 +/- 27 and 76 +/- 40-mu-g l-1 (P < 0.001), respectively. Neither ranitidine nor cimetidine produced statistically significant changes in the pharmacological response to nifedipine.