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.
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D001853:Bone Marrow / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D003404:Creatinine / Q000652:urine; D003524:Cyclosporins / Q000633:toxicity*; D004357:Drug Synergism; D005839:Gentamicins / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D051381:Rats; D013997:Time Factors; D014508:Urea / Q000097:blood
D001798:Blood Proteins; D003524:Cyclosporins; D005839:Gentamicins; D014508:Urea; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000118:Acetylglucosaminidase