Pharmacokinetics
Pharmacokinetic data after single dose palbociclib were collected and analyzed for a total of 34 patients (7 at 50 mg/m2, 21 at 75 mg/m2, and 6 at 95 mg/m2). Data after repeated palbociclib doses were available for a total of 27 patients (6 at 50 mg/m2, 18 at 75 mg/m2, and 3 at 95 mg/m2). The palbociclib plasma concentration-time profiles are depicted for each dosing group in Supplementary Figure S1 , and the associated pharmacokinetic parameters are reported in Table 6 .
Palbociclib was absorbed with a mean Tmax between 4.9 and 6.6 h post-dose, and exhibited an elimination with a mean half-life between 11.3 and 19.5 h and a mean apparent oral clearance ranging from 26.8 and 52.6 L/h/m2. Within 50 and 95 mg/m2, following single and repeated doses, mean palbociclib Cmax and AUC0-Tlastincreased in proportional manner; however, large inter-individual variabilities were observed among the pharmacokinetic parameters.