Chronopharmacokinetics and calcium in the prevention of gentamicin-induced nephrotoxicity in rabbits

The study used 36 New Zealand white rabbits organized into three groups of 12 animals each. Group I received gentamicin; Group II received joint administration of gentamicin and calcium chloride and Group III received gentamicin, calcium chloride and verapamil. All the drugs were administered over 16 day periods. Groups I and II were divided in two subgroups, one subgroup receiving the treatment in winter and the other in summer. The results obtained for Group I indicate that there is an influence of the seasonal period on the gentamicin elimination and/or distribution. Mean plasma levels of the antibiotic at steady-state as well as the amounts of gentamicin accumulated in renal tissue are higher in winter than in summer. On the other hand, when calcium was administrated with the antibiotic, no significant circannual variations were observed in the renal toxicity of gentamicin. Under our study conditions the presence of calcium diminishes gentamicin plasma levels and the amount accumulated in kidney. Calcium, probably, generated a diminution in renal damage and consequently gentamicin renal excretion increases. The differences between Group II and Group III are due to the effect of verapamil. This agent blocks the calcium channels reducing the calcium protective effect on the nephrotoxicity of gentamicin. © 1998 John Wiley & Sons, Ltd.