ArticleThe Kaohsiung journal of medical sciences2016
Dosing-time contributes to chronotoxicity of clofarabine in mice via means other than pharmacokinetics.
Article in The Kaohsiung journal of medical sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 3 citations in OpenAlex.
- Chronotherapy in Hematological Malignancies: Evaluating the Rationale and Evidence.Pharmacology research & perspectives · 2026Review
- Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective.Cancers · 2022Review
- Molecular Aspects of Circadian Pharmacology and Relevance for Cancer Chronotherapy.International journal of molecular sciences · 2017Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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, LD50s, 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 LD50. 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.