Circadian rhythm in tolerance of mice for etoposide.

Etoposide (40 mg/kg/day X 3 days and 60 mg/kg/day X 3 days) was best tolerated by male B6D2F1 mice when given in the second half of the rest span of their sleep-wake circadian cycle. Such a time-qualified treatment resulted in increased long-term survival rate, highest peripheral leukocyte count at nadir, and lowest body weight loss, as compared to results from drug dosing in the activity span. Assuming that such results may be extrapolated to human beings, the treatment time of etoposide associated with an optimal tolerance would be located in the second half of the sleeping span (usually near 5.00 hrs).