Palbociclib (PD-0332991) pharmacokinetics in subjects with impaired renal function

Purpose This publication describes an evaluation of the impact of different degrees of renal impairment on the pharmacokinetics and safety of palbociclib after a single 125-mg oral dose. Methods Thirty-one subjects were assigned to different renal function groups. Serial blood sampling for pharmacokinetics was performed up to 120 h and 168 h post-palbociclib dose for subjects with normal and impaired renal function, respectively. A separate blood sample was collected at pre-dose and 8 h after dosing to measure plasma protein binding. Plasma palbociclib was measured using a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. Plasma protein binding samples were processed by equilibrium dialysis and measured by a validated LC–MS/MS method. Results Plasma palbociclib exposure was higher in subjects with renal impairment than in subjects with normal renal function; however, there were no marked differences in exposure across subjects with mild, moderate, and severe renal impairment. Total plasma exposure AUC inf increased by 39%, 42%, and 31% with mild, moderate, and severe renal impairment, respectively, relative to subjects with normal renal function. Peak exposure C max increased by 17%, 12%, and 15% for mild, moderate, and severe impairment, respectively. There was no obvious trend in the mean f u with worsening renal function. The PBPK model adequately described palbociclib exposure observed in subjects with moderate or severe renal impairment from this study. Conclusion Palbociclib was safe and well-tolerated in a small population of subjects with normal and impaired renal function after a single oral 125 mg dose. No dose adjustment is required in patients with renal impairment.