The toxic effects of combined administration of cyclosporin A and gentamicin.

The toxic properties of cyclosporin A and gentamicin give alone and in combination were investigated in groups of Sprague-Dawley rats over a 7-day period. Administration of each drug on its own caused minor impairment of renal and hepatic function: cyclosporin A had additional structural effects on renal tubules and lymphoid tissue. Combined therapy resulted in acute renal failure with two distinct zones of damage in the renal proximal tubules--gentamicin-induced necrosis of the convoluted segment and cyclosporin A-related vacuolation of the straight segment--and the effects on hepatic and haematological parameters were more pronounced. The results indicate the need for caution before cyclosporin A and another potentially nephrotoxic drug and administered together and for specific monitoring or renal function where such combined therapy is considered essential.