EFFECTS OF CALCIUM-CHANNEL BLOCKERS ON RENAL-FUNCTION IN MICE

Tumor blood flow modification is currently under investigation as a possible means of optimizing current cancer therapies, with particular respect to improving the efficacy of bioreductive agents. A variety of calcium channel blockers have been shown to modify tumor perfusion in model systems, and may be valuable as potentiators of both bioreductive and conventional drugs. We report the effects of nifedipine, verapamil, flunarizine, and cinnarizine on renal function in C3H mice, assayed by clearance of simultaneously injected Cr-51 ethylenediamine tetraacetate. Nifedipine at 10 mgkg-1 blocked Cr-51 ethylenediamine tetraacetate clearance for 30 min and reduced its subsequent rate of clearance by a factor (+/- 2 se) of 2.4 +/- 0.6. At 1 mgkg-1 it reduced the rate of clearance by a factor of 1.2 +/- 0.2. Verapamil at 10 mgkg-1 blocked Cr-51 ethylenediamine tetraacetate clearance for 10 min and reduced its subsequent rate of clearance by a factor of 1.5 +/- 0.3, but had no effect at 1 mgkg-1. Flunarizine had no effect at 50 mgkg-1 or at 5 mgkg-1, but cinnarizine at 50 mgkg-1 reduced clearance rate by a factor of 1.2 +/- 0.1. The data show that some of these vasoactive agents, nifedipine and verapamil in particular, can severely compromise renal function and may, therefore, affect the plasma pharmacokinetics of co-administered drugs that are cleared by the kidney.