In:
The Kaohsiung Journal of Medical Sciences, Wiley, Vol. 32, No. 5 ( 2016-05), p. 227-234
Abstract:
To evaluate the time‐ and dose‐dependent toxicity of clofarabine in mice and to further define the chronotherapy strategy of it in leukemia, we compared the mortality rates, LD 50 s, biochemical parameters, histological changes and organ indexes of mice treated with clofarabine at various doses and time points. Plasma clofarabine levels and pharmacokinetic parameters were monitored continuously for up to 8 hours after the single intravenous administration of 20 mg/kg at 12:00 noon and 12:00 midnight by high performance liquid chromatography (HPLC)‐UV method. Clofarabine toxicity in all groups fluctuated in accordance with circadian rhythms in vivo . The toxicity of clofarabine in mice in the rest phase was more severe than the active one, indicated by more severe liver damage, immunodepression, higher mortality rate, and lower LD 50 . No significant pharmacokinetic parameter changes were observed between the night and daytime treatment groups. These findings suggest the dosing‐time dependent toxicity of clofarabine synchronizes with the circadian rhythm of mice, which might provide new therapeutic strategies in further clinical application.
Type of Medium:
Online Resource
ISSN:
1607-551X
,
2410-8650
DOI:
10.1016/j.kjms.2016.04.001
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2202782-8
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