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Circadian changes in mitoxantrone toxicity in mice: Relationship with plasma pharmacokinetics

✍ Scribed by Francis Lévi; Marco Tampellini; Gérard Metzger; Ernest Bizi; Guy Lemaigre; Michael Hallek

Publisher
John Wiley and Sons
Year
1994
Tongue
French
Weight
631 KB
Volume
59
Category
Article
ISSN
0020-7136

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✦ Synopsis

Circadian time-dependent differences in clinical toxicity of several anti-cancer agents were predicted from murine studies. Mitoxantrone is an anthracenedion (an anthracycline-related class of compounds) of increased clinical use, which may benefit from selective circadian timing. In 3 consecutive studies, a total of 428 male B6D2FI mice aged from 8 to 10 weeks were synchronized by an alternation of I 2 hr of light and I 2 hr of darkness (LD 12:12). They received a single i.v. injection of mitoxantrone at one of 6 or 4 circadian stages differing by 4 or 6 hr. A dose-response relationship characterized body-weight loss and survival rate. Dose-toxicity relationship further closely depended upon circadian dosing time. Thus, a dose of 16 mg/kg killed 100% of the mice injected at 3 hr after light onset

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