title: Potentiated nephrotoxicity of cisplatin when combined with amikacin comparing young and adult rats.
abstract: We compared the nephrotoxic interaction between cisplatin (CP) and amikacin (AM) in young and adult rats, using different dosage combinations. Following a single i.v. dose of CP, AM was administered s.c. for 14 days. The dose of CP was chosen to cause a 20%-50% fall in the glomerular filtration rate (GFR), while a dose of AM was chosen that had only a minimal effect on GFR. In adult rats, a decrease in GFR to 60% of the control value after CP alone was seriously aggravated by a non-toxic AM course given during 2 weeks after CP. In this combination, the GFR per 100 g body weight was reduced to 30% of control at week 2, which rose to 40% of control at week 15. In young rats, a non-toxic AM course did not aggravate the CP-induced impairment in GFR. However, when the dose of AM was increased to cause a 20% reduction in the GFR, the nephrotoxicity was potentiated. When measured at week 2, the GFR per 100 g body weight was 40% of control after the combined treatment compared with 80% of control after CP alone. As in adult rats, there was only a partial recovery of the GFR. In conclusion, in both adult and young rats, a course of AM following a single injection of CP potentiated CP-induced nephrotoxicity.
authors.affiliation: Department of Pediatric Surgery, Erasmus University, Rotterdam, The Netherlands.
authors.forename: H T
authors.initials: HT
authors.lastname: Jongejan
authors.forename: A P
authors.initials: AP
authors.lastname: Provoost
authors.forename: J C
authors.initials: JC
authors.lastname: Molenaar
mesh_terms: D000375:Aging / Q000502:physiology*; D000583:Amikacin / Q000633:toxicity*; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004357:Drug Synergism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000583:Amikacin; D002945:Cisplatin