ATP-MgCl sub(2) increases cisplatin toxicity in the dog and rat

The purpose of this study was to examine if ATP-MgCl sub(2), an agent that protects against acute cisplatin toxicity in vitro, protected against cisplatin toxicity in vivo. Baseline renal function measurements were obtained on dogs (n = 12) and rats (n = 20) and rats (n = 20) on day -1. Dogs were given 90 mg m super(-2) cisplatin (n = 5), 90 mg m super(-2) cisplatin and 50 mu mol/kg ATP-MgCl sub(2) (n = 5), or 90 mg m super(-2) cisplatin and 150 mu mol/kg ATP-MgCl sub(2) (n = 2), in a slow bolus i.v. injection on day 0. Rats were given 4 mg/kg cisplatin i.p. (n = 6) and 25 mu mol kg ATP-MgCl sub(2) (n = 8) i.v. or 4 mg/kg cisplatin i.p. and 25 mu mol/kg ATP-MgCl sub(2) (n = 6) i.v. on day 0. Renal function was assessed on a routine basis for 14 days. All dogs had significantly decreased creatinine clearance following cisplatin administration. There were no significant differences in renal function tests between groups of dogs. One dog given 50 mu mol/kg ATP-MgCl sub(2) and both dogs given 150 mu mol/kg ATP-MgCl sub(2) in addition to cisplatin developed acute anuric renal failure and were euthanatized prior to completion of the study.