CHANGES IN RENAL HANDLING OF PLATINUM IN CISPLATINUM-TREATED RATS FOLLOWING INDUCTION OF METABOLIC-ACIDOSIS OR ALKALOSIS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 36  (2) , 273-285
Abstract
Manipulations of metabolic acid-base status were used in an attempt to modify the renal handling and toxicity of the anticancer drug cis-platinum. Rats were orally pretreated with tap water (TW), ammonium chloride (AC) or sodium bicarbonate (SB) for 3 days prior to i.p. administration of a high cis-platinum dose (7.5 mg/kg body weight). Urine was collected daily for 4 days between drug dosing and killing of the animals. AC-pretreated rats did not exhibit the characteristic cis-platinum-induced diuresis and were unable to maintain an acid urinary pH following drug administration. AC rats had a significantly lower, and SB rats a significantly higher, urinary excretion of Pt than did TW rats. Pt excretion was correlated with urinary pH (r = 0.88) and not urinary volume (r = 0.30). The renal concentration of Pt was greater in AC animals than in SB or TW animals, but no significant difference was observed in liver or plasma concentrations between the groups. Both pretreated groups had equal percent of free vs. bound Pt. Proteinuria was more severe in AC-pretreated rats, but histologic evidence of renal tubular damage was present in all 3 groups. Metabolic acidosis can seriously impair the renal handling of high dose cis-platinum but metabolic alkalosis offers no evident advantages over non-pretreatment.