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Chronotoxicity of nedaplatin in rats.

Abstract
Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00h than 08:00h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.
AuthorsYimin Cui, Koh-Ichi Sugimoto, Yoshiko Kawai, Toshiaki Sudoh, Munekazu Gemba, Akio Fujimura
JournalChronobiology international (Chronobiol Int) Vol. 21 Issue 4-5 Pg. 601-11 (Jul 2004) ISSN: 0742-0528 [Print] England
PMID15470957 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Organoplatinum Compounds
  • nedaplatin
  • Creatinine
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacokinetics, toxicity)
  • Bone Marrow (drug effects, metabolism)
  • Chronotherapy
  • Circadian Rhythm (physiology)
  • Creatinine (metabolism)
  • Kidney Cortex (drug effects, metabolism)
  • Leukocyte Count
  • Male
  • Organoplatinum Compounds (administration & dosage, pharmacokinetics, toxicity)
  • Photoperiod
  • Rats
  • Rats, Sprague-Dawley
  • Weight Gain (drug effects)

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