CHRONOPHARMACOKINETICS AND CALCIUM IN THE PREVENTION OF GENTAMICIN-INDUCED NEPHROTOXICITY IN RABBITS

The study used 36 New Zealand white rabbits organized into three group s of 12 animals each. Group I received gentamicin; Group Il received j oint administration of gentamicin and calcium chloride and Group III r eceived 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 oth er 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 h igher in winter than in summer. On the other hand, when calcium was ad ministrated with the antibiotic, no significant circannual variations were observed in the renal toxicity of gentamicin. Under our study con ditions the presence of calcium diminishes gentamicin plasma levels an d the amount accumulated in kidney. Calcium, probably, generated a dim inution in renal damage and consequently gentamicin renal. excretion i ncreases. The differences between Group II and Group III are due to th e effect of verapamil. This agent blocks the calcium channels reducing the calcium protective effect on the nephrotoxicity of gentamicin. (C ) 1998 John Wiley & Sons, Ltd.