14

Diltiazem increases nifedipine levels 'Diltiazem pretreatment resulted in a marked

increase in the plasma level of nifedipine and enhanced the hemodynamic effect of nifedipine.'

Nifedipine and diItiazem may be useful in combined therapy for angina, but diltiazem may inhibit the hepatic metabolism of nifedipine. Therefore, the effect of 3 days of pretreatment with oral diltiazem 60mg tid or placebo on an oral dose of nifedipine 20mg was studied in 6 healthy males in a double-blind, crossover trial.

With diItiazem, mean plasma nifedipine levels were significantly higher for 10 hours after dosing except at 20 min. The AUC for nifedipine was increased by 140% after diltiazem but there was no change in maximum plasma concentration (Cmax) or time of Cmax. The half-life of nifedipine was increased from 2.46 to 3.21 hours after diltiazem compared with placebo, and there was a significant decrease in total body clearance (Cl). Diltiazem did not significantly affect the AUe, half-life or Cl of the acid metabolite of nifedipine, and there was no significant effect on the elimination rate constant for indocyanine green. BP was significantly lower after nifedipine and diltiazem compared with nifedipine and placebo. Ohashi K. Tateishi T , Sudo T. Sakamoto K, Toyosak i N . et al. Effects of diltiazem on the pharmacokinetics of nifcdipine. Journal of Cardiovascular Pharmacology 15: 96-10 I, Jan 1990 ""

10 Feb 1990 INPHARMA@ 0156-2703/ 90/ 0210-0014/ 0$01.00/ 0 © ADIS Presl