Comparative nephrotoxicity of carboplatin and cisplatin in combination with tobramycin.
The nephrotoxic potentials of cisplatin and carboplatin, alone and in combination with the aminoglycoside antibiotic tobramycin, were compared in male rats. Sixty (60) male Sprague-Dawley rats were divided into six groups of ten rats each and received the following treatments: Group I, saline; group II, cisplatin (5 mg/kg); group III, cisplatin (5 mg/kg) + tobramycin (50 mg/kg); group IV, carboplatin alone (50 mg/kg); group V, carboplatin (50 mg/kg) + tobramycin (50 mg/kg); and group VI, tobramycin alone (50 mg/kg). Carboplatin and cisplatin were each administered as a single i.v. injection on day 1. Tobramycin was administered i.-m. once daily on days 1-5. All rats were euthanatized on day 6. Smaller body weight gains occurred in groups II-V than in saline controls. Serum urea nitrogen (BUN) levels recorded on day 6 were elevated in group III. BUN values of all other groups were normal. Histopathologic examination of kidneys revealed acute tubular injury in rats treated with cisplatin, whether alone or in combination with tobramycin, and in carboplatin/tobramycin-treated rats. Carboplatin and tobramycin, when administered separately, were not nephrotoxic. The combination of cisplatin and tobramycin proved to be the most nephrotoxic treatment.
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D016190:Carboplatin; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014031:Tobramycin / Q000008:administration & dosage / Q000633:toxicity*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin; D002945:Cisplatin; D014031:Tobramycin