Potentiated nephrotoxicity of cisplatin when combined with amikacin comparing young and adult rats.
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.
Jongejan
H T
HT
Department of Pediatric Surgery, Erasmus University, Rotterdam, The Netherlands.
Provoost
A P
AP
Molenaar
J C
JC
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
D000583:Amikacin; D002945:Cisplatin