A comparison of the effects of cisplatin and N-methyliminodiacetato-(1,2-diaminocyclohexane)-platinum(II) on renal function and gentamicin excretion in rats

Toxicology. 1987 Dec 14;47(3):307-15. doi: 10.1016/0300-483x(87)90060-6.

Abstract

N-methyliminodiacetato(1,2-diaminocyclohexane)-platinum(II) (MIDP) is a new third-generation water-soluble antitumor platinum complex. This study compares the effects of MIDP (3 injections of 25 mg/kg each on days 1, 5 and 9) on renal structure and function and the urinary excretion of gentamicin (GENT) with those of a single 6 mg/kg dose of cisplatin (DDP) in F-344 (Fischer) rats. GENT was given as a single dose of 30 mg/kg 7 days after DDP injection or the last MIDP injection. Rats given DDP and GENT had significantly different plasma urea nitrogen (BUN) levels (315 +/- 79 mg/dl) and creatinine clearance (0.40 +/- 0.24 ml/[min.kg]) than did the control group that was given only GENT (15 +/- 1 mg/dl and 5.5 +/- 0.6 ml/[min.kg]). MIDP did not affect renal function (BUN, 16 +/- 3 mg/dl; creatinine clearance, 6.1 +/- 1.0 ml/[min.kg]). Light microscopic examination of renal tissue from MIDP-treated rats did not reveal any evidence of cell degeneration or necrosis. Rats given GENT alone excreted 72 +/- 4% of the dose in 24 h and had plasma gentamicin levels of 19 +/- 2 ng/ml 24 h after injection. The group pretreated with DDP had lower urinary GENT excretion (31 +/- 10%) and higher plasma GENT levels (7491 +/- 3750 ng/ml). MIDP pretreatment had no effect on GENT excretion (72 +/- 8%) or plasma GENT levels (16 +/- 2 ng/ml). Thus, MIDP did not cause any measureable decrease in renal function or GENT excretion in our study. Since nephrotoxicity is a significant problem with DDP administration, further studies with MIDP are warranted.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Blood Urea Nitrogen
  • Cisplatin / toxicity*
  • Creatinine / metabolism
  • Gentamicins / urine*
  • Kidney / drug effects*
  • Kidney / physiology
  • Male
  • Organoplatinum Compounds / toxicity*
  • Rats
  • Rats, Inbred F344

Substances

  • Antineoplastic Agents
  • Gentamicins
  • Organoplatinum Compounds
  • N-methyliminodiacetato-1,2-diaminocyclohexane platinum(II)
  • Creatinine
  • Cisplatin