Chronotoxicity of nedaplatin in rats.
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.
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Yimin
Y
Cui
Koh-Ichi
K
Sugimoto
Yoshiko
Y
Kawai
Toshiaki
T
Sudoh
Munekazu
M
Gemba
Akio
A
Fujimura
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D019454:Chronotherapy; D002940:Circadian Rhythm / Q000502:physiology*; D003404:Creatinine / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D017440:Photoperiod; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin; D003404:Creatinine