Cancer Chemotherapy and Pharmacology

, Volume 79, Issue 3, pp 527–533 | Cite as

Effect of food on the bioavailability of palbociclib

  • Ana Ruiz-Garcia
  • Anna Plotka
  • Melissa O’Gorman
  • Diane D. Wang
Original Article

Abstract

Purpose

This phase I study estimated the effect of food on bioavailability of palbociclib (IBRANCE®), and a selective inhibitor of cyclin-dependent kinase 4/6 approved for oncology indications has pH-dependent solubility and high permeability.

Methods

In this randomized, four-sequence, four-period crossover study, 28 healthy volunteers received a single 125-mg dose of palbociclib (free-base capsule) following an overnight fast or (1) after a high-fat/-calorie meal, (2) after a low-fat/-calorie meal, and (3) between two moderate-fat/standard-calorie meals. Pharmacokinetic samples were collected predose and serially ≤144 h postdose; palbociclib concentrations were measured using validated high-performance liquid chromatography tandem mass spectrometry. Pharmacokinetic data were analyzed using a noncompartmental approach based on a mixed-effects model.

Results

Median time to maximum concentration was 8 h for all conditions. Exposure (AUCinf and C max) increased slightly in the fed versus fasted conditions; ratios (90% CIs) of the adjusted geometric mean relative to the fasted condition ranged from 111.8 (104.3–119.9%) to 120.6% (112.6–129.1%) for AUCinf and from 124.0 (108.4–141.9%) to 137.8% (120.6–157.5%) for C max due mainly to three subjects with significantly lower exposure (low liers) in the fasted condition. Pharmacokinetic variability was reduced in the fed (AUCinf, 23–27%; C max, 21–24%) versus fasted (AUCinf, 39%; C max, 73%) conditions. In a supplemental analysis excluding the three low liers, food intake did not affect palbociclib exposure.

Conclusions

Food intake modestly increased palbociclib exposure while greatly reducing pharmacokinetic variability. For subjects with normal absorption, food intake did not affect palbociclib exposure. Thus, palbociclib should be administered with food.

Trial registration

ClinicalTrials.gov: NCT01904747.

Keywords

Palbociclib CDK4/6 inhibitor Phase I Bioavailability Pharmacokinetics Food effect 

Notes

Acknowledgements

The authors would like to thank the study volunteers. Editorial support was provided by Johna Van Stelten, PhD, of Complete Healthcare Communications, LLC, and was funded by Pfizer Inc.

Author contribution

AR-G, AP, MO, and DW wrote manuscript, designed research, performed research, analyzed data, and contributed new agents/analytical tools.

Compliance with ethical standards

Conflict of interest

This study (A5481021; NCT01904747) was sponsored by Pfizer Inc. All authors are employees of and shareholders in Pfizer Inc.

Supplementary material

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Supplementary material 1 (PS 2960 KB)
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Supplementary material 2 (PS 3462 KB)
280_2017_3246_MOESM3_ESM.docx (22 kb)
Supplementary material 3 (DOCX 21 KB)
280_2017_3246_MOESM4_ESM.docx (21 kb)
Supplementary material 4 (DOCX 20 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Pfizer IncSan DiegoUSA
  2. 2.Pfizer IncCollegevilleUSA
  3. 3.Pfizer IncGrotonUSA

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