Immediate and prolonged effects of drugs on rhythm's characteristics: Relevance to chronochemotherapy

Four groups of mice were injected with vincristine, each at a different time, for ten successive days. Mortality and daily pattern of peripheral white blood cells (WBC) count were monitored immediately and at various times after the last injection. The results demonstrated that (1) drug administration time dependency was observed in rate of death, recorded for 80 days following the injections; (2) the time of drug administration affected the parameters of WBC count rhythm, and (3) there were differences between immediate effects upon the rhythm parameters (monitored one day after the last injection) to those measured at succeeding times (on days 8 and 15 after injections cessation). The results emphasize the need to consider continuous post administration rhythm changes, especially when scheduling repeated chronotherapeutics, where variables which serve for toxicity-diagnosis are rhythmic in nature.