Effect of a forced diuresis on the distribution and excretion (via urine and bile) of 195mplatinum when given as 195mplatinum cis-dichlorodiammineplatinum(II)

Abstract

195mPlatinum cis-dichlorodiammineplatinum(II) (195mPt cis-DDP) was injected iv with furosemide or mannitol into male Sprague-Dawley rats. The effect of such a diuresis on the distribution, excretion, and retention of cis-DDP was measured. The mannitol-treated animals had a significant increase in the urinary excretion of 196mPt over control animals for the first five 15-minute collection times and for the 24-hour cumulative urine for the 0.01-mg/kg dose. At the 6-mg/kg dose, only the first three 15-minute and 24-hour cumulative urine collections were significant. This increased excretion, however, did not affect tissue or blood concentrations of this agent. Furosemide did not affect the excretion of 195mPt. A biliary excretion of 195mPt given as 195mPt cis-DDP is documented. The excretion is biphasic, with a rapid phase followed by a slower protracted phase. Forced diuresis, if it affords renal protection, does so during the first 90 minutes of urinary excretion.