CISPLATIN URINARY PHARMACOKINETICS AND NEPHROTOXICITY - A COMMON CIRCADIAN MECHANISM

  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (11) , 1933-1938
Abstract
Renal toxicity and urinary pharmacokinetics following a nonlethal dose (5 mg/kg) of [the antineoplastic drug] cisplatin were investigated in female F344 (Fischer) rats that were on a standardized light-dark schedule, with water freely available. Circadian timing of drug administration had a major effect on the BUN [blood urea N] increase (P < 0.01), the urine volume increase (P < 0.025) and the urinary concentration of cisplatin following drug administration (P < 0.01). Renal toxicity was postively correlated with the peak urinary concentration of cisplatin and with the area under the curve of urinary concentration over the 1st 20 h after drug administration (P < 0.01). Drug administration near the normal circadian maximum of urinary volume prior to treatment resulted in the least renal toxicity, lowest peak and smallest area of urinary concentration of cisplatin.