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Effects of calcium channel blockers on renal function in mice

D J Honess1, N M Bleehen

  • 1Medical Research Council, Cambridge, UK.

International Journal of Radiation Oncology, Biology, Physics
|January 1, 1992
PubMed

Insights

Certain calcium channel blockers, like nifedipine and verapamil, can impair kidney function in mice. This impacts how the body processes drugs cleared by the kidneys, potentially affecting cancer therapy efficacy.

Area of Science:

  • Pharmacology
  • Nephrology
  • Oncology

Background:

  • Tumor blood flow modification is explored to enhance cancer therapies, especially bioreductive agents.
  • Calcium channel blockers (CCBs) are investigated for their potential to alter tumor perfusion and potentiate drug efficacy.

Purpose of the Study:

  • To evaluate the effects of specific CCBs (nifedipine, verapamil, flunarizine, cinnarizine) on renal function in C3H mice.
  • To assess the impact of these CCBs on the clearance of 51Cr ethylenediamine tetraacetate as a measure of kidney function.

Main Methods:

  • Renal function was assayed in C3H mice using the clearance of simultaneously injected 51Cr ethylenediamine tetraacetate.
  • Mice were administered varying doses of nifedipine, verapamil, flunarizine, and cinnarizine.

Main Results:

  • Nifedipine (10 mg/kg) significantly reduced 51Cr EDTA clearance for 30 minutes and decreased its subsequent rate.
  • Verapamil (10 mg/kg) transiently blocked 51Cr EDTA clearance and reduced its subsequent rate; lower doses had no effect.
  • Flunarizine showed no significant effect on renal clearance, while cinnarizine (50 mg/kg) caused a minor reduction.

Conclusions:

  • Nifedipine and verapamil can significantly impair renal function in mice at tested doses.
  • The observed renal effects suggest these CCBs may alter the pharmacokinetics of co-administered drugs cleared by the kidney.
  • These findings highlight potential challenges in combining certain CCBs with other cancer therapies due to renal effects.

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