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(Hypertension. 1996;28:109-114.)
© 1996 American Heart Association, Inc.

Articles

Comparison of Nifedipine Alone and With Diltiazem or Verapamil in Hypertension

Joseph J. Saseen; Barry L. Carter; Thomas E.R. Brown; William J. Elliott; Henry R. Black

the University of Colorado Health Science Center, Department of Pharmacy Practice, Denver, Colo (J.J.S., B.L.C.); Health Sciences Center, Department of Pharmaceutical Services, Winnipeg, Manitoba, Canada (T.E.R.B.); and Department of Preventive Medicine, Rush-Presbyterian–St Luke's Medical Center, Chicago, Ill (W.J.E., H.R.B.).

Correspondence to Barry L. Carter, University of Colorado Health Science Center, Department of Pharmacy Practice, School of Pharmacy, Box C238, 4200 E Ninth Ave, Denver, CO 80262.

Receptor binding studies suggest that combinations of calcium channel blockers may result in either enhanced or diminished pharmacological effects, but clinical data in hypertension are incomplete. In this study, we compared blood pressure reductions using nifedipine alone, nifedipine plus diltiazem, and nifedipine plus verapamil and determined whether combinations alter nifedipine pharmacokinetics. After determination of baseline blood pressures, 16 subjects with essential hypertension (12 men, 4 women; mean age, 48 years) received 30 mg/d open-label, sustained release nifedipine for 2 weeks. If still hypertensive (n=16), they were randomized (double-blind) to receive either additional sustained release diltiazem or sustained release verapamil, both 180 mg/d, for 2 weeks and were then crossed-over for the final 2 weeks of the study. All medications were once-daily, extended-release formulations. Blood pressures and nifedipine plasma concentrations were measured during the final day of each treatment. Overall, each combination lowered mean systolic and diastolic pressures more than nifedipine alone. Mean supine diastolic pressures were significantly lower at 8 hours (77.6 versus 84.6 mm Hg, P=.001) and 12 hours (81.5 versus 87.1 mm Hg, P=.04) with nifedipine plus diltiazem than nifedipine plus verapamil. Mean nifedipine concentrations were inversely correlated with mean blood pressures. Mean nifedipine area under the curve values were greater with diltiazem than verapamil (1430 versus 1134 ng·h/mL, P=.026), with each greater than nifedipine alone (957 ng·h/mL). Nifedipine plus diltiazem had a greater antihypertensive effect than nifedipine plus verapamil. Diltiazem caused greater increases in nifedipine plasma concentrations than did verapamil. These data suggest that combined calcium channel blockers result in additive antihypertensive effects, perhaps because of a pharmacokinetic interaction.

Key Words: blood pressure • pharmacokinetics • drug therapy, combination • calcium channel blockers

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