Dose Schedule Optimization and the Pharmacokinetic Driver of Neutropenia
Figure 5
Moving average PK describes rat neutrophil counts.
Rat neutrophil counts were measured response to the investigational PLK inhibitor TAK-960 and the relationship between plasma PK and neutrophil nadir was assessed. A) Absolute Neutrophil Count (ANC) normalized to control group plotted over the course of 21 days on a variety of dosing regimens. B) Normalized ANC nadir plotted versus total cycle AUC for each schedule tested. C) Normalized ANC nadir plotted versus the Cmax for each schedule tested. D) R2 plotted for Cavg,ndays for n-days from 1 to 14 days. E) The corresponding p-values of the Cavg,ndays correlation showing correlation. F) Normalized ANC nadir is highly correlated with max(Cavg,4days) with R2 = 0.70 (p<0.05), a better correlation than either Cmax or AUC.