Chronotoxicity and Chronopharmacokinetics of Methotrexate in Mice Modification by Feeding Schedule

Jian Guo Song, Shigehiro Ohdo, Nobuya Ogawa, Shigeyuki Nakano

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The circadian rhythms of the toxicity and the pharmacokinetics of methotrexate (MTX), as well as the effects of manipulation of feeding schedule on the rhythms, were investigated in mice. Male ICR mice were housed under a standardized light-dark cycle (12:12) with food and water ad libitum (ALF) or under the time-restricted feeding (TRF) schedule (8 hr during the light phase) for 1 day or 14 days before the drug administration. The animals received MTX (100 mg/kg, i.p.) once daily for 7 days in the toxicity studies and a single dose of MTX (100 mg/kg, i.p.) for the kinetic studies. Under the ALF, a significant dosing time dependency was demonstrated for the toxicity of MTX with a longer survival time for the middark dosing and a shorter one for the midlight dosing. The MTX kinetics also showed a significant rhythm, with the highest clearance at middark and the lowest one at midlight. The rhythm in MTX kinetics well coincided with that in the toxicity of the drug. The TRF had a marked influence on the rhythms of MTX kinetics and toxicity. Thus, the timing of dosing is important in the kinetics and the toxicity of MTX in mice, and the manipulation of feeding schedule can modify the rhythm of the toxicity by changing that of the MTX kinetics.

Original languageEnglish
Pages (from-to)373-378
Number of pages6
JournalThe Japanese Journal of Pharmacology
Volume62
Issue number4
DOIs
Publication statusPublished - Jan 1 1993

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Methotrexate
Appointments and Schedules
Chronopharmacokinetics
Inbred ICR Mouse
Photoperiod
Circadian Rhythm
Drug-Related Side Effects and Adverse Reactions
Pharmacokinetics
Light
Food
Water
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Chronotoxicity and Chronopharmacokinetics of Methotrexate in Mice Modification by Feeding Schedule. / Song, Jian Guo; Ohdo, Shigehiro; Ogawa, Nobuya; Nakano, Shigeyuki.

In: The Japanese Journal of Pharmacology, Vol. 62, No. 4, 01.01.1993, p. 373-378.

Research output: Contribution to journalArticle

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