IMMEDIATE AND PROLONGED EFFECTS OF DRUGS ON RHYTHMS CHARACTERISTICS -RELEVANCE TO CHRONOCHEMOTHERAPY

Four groups of mice were injected with vincristine, each at a differen t time, for ten successive days. Mortality and daily pattern of periph eral white blood cells (WBC) count were monitored immediately and at v arious times after the last injection. The results demonstrated that(1 )drug administration time dependency was observed in rate of death, re corded for 80 days following the injections; (2) the time of drug admi nistration 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 succ eeding times (on days 8 and 15 after injections cessation). The result s emphasize the need to consider continuous post administration rhythm changes, especially when scheduling repented chronotherapeutics, wher e variables which serve for toxicity-diagnosis are rhythmic in nature.