Nature Medicine
7, 356 - 360 (2001)
doi:10.1038/85507
Changing the dosing schedule minimizes the disruptive effects of interferon on clock functionShigehiro Ohdo1, Satoru Koyanagi1, 2, Hinako Suyama1, Shun Higuchi1
& Hironori Aramaki31
Department of Clinical Pharmacokinetics, Division of Pharmaceutical Sciences, Graduate School, Kyushu University, Higashi-Ku, Fukuoka, Japan
2
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-Ku, Fukuoka, Japan
3
Department of Molecular Biology, Daiichi College of Pharmaceutical Sciences, Minami-Ku, Fukuoka, Japan
Correspondence should be addressed to Shigehiro Ohdo ohdo@phar.kyushu-u.ac.jpThe effectiveness and toxicity of many drugs vary depending on the relationship between the dosing schedule and the 24-hour rhythms of biochemical, physiological and behavioral processes. In addition, several drugs can cause alterations to the 24-hour rhythms leading to illness and altered homeostatic regulation. However, the mechanisms of this drug-based disruption of circadian 'clock' genes remain unclear. Here, we show the disruptive effect of interferon- on the rhythm of locomotor activity, body temperature and clock-gene mRNA expression in the periphery and suprachiasmatic nuclei, a primary circadian pacemaker. The rhythmicity of clock genes and the photic induction of the Per gene in suprachiasmatic nuclei were disturbed by the repetitive administration of interferon-. Moreover, alteration of clock function, a new concept of adverse effects, can be overcome by optimizing the dosing schedule to minimize adverse drug effects.
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