The effects of manipulation of feeding schedule on the circadian rhythms of toxicity and pharmacokinetics of theophylline were studied in mice. Male ICR mice were housed in a standardized light-dark (LD) cycle (LD 12:12) with food and water ad libitum or under the time-restricted feeding schedule (feeding time: 8 hours during light phase) for 2 weeks. Each animal was given 215 mg/kg theophylline intraperitoneally for toxicity studies and 80 mg/kg dose of the drug for pharmacokinetic studies. Under the ad libitum feeding schedule, a highly significant circadian rhythm was demonstrated in mortality depending on the time of injection with the highest mortality during light phase and the lowest during dark phase. The time-restricted feeding schedule had a marked influence on the rhythm of theophylline toxicity, showing higher mortality during dark phase and lower mortality during light phase. Since the rhythm in theophylline kinetics nicely corresponded to the toxicity rhythm, the rhythm of toxicity seems to be, at least partly, due to the rhythm in the pharmacokinetics. Manipulation of feeding schedule has a marked influence on the rhythms of acute toxicity and kinetics of theophylline in mice.
|Number of pages
|Annual Review of Chronopharmacology
|Published - 1988
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