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Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 1, pp 139–146 | Cite as

Inter- and intra-patient variability in pharmacokinetics of abiraterone acetate in metastatic prostate cancer

  • Malmaruha ArasaratnamEmail author
  • Megan Crumbaker
  • Atul Bhatnagar
  • Matthew J. McKay
  • Mark P. Molloy
  • Howard Gurney
Original Article
  • 83 Downloads

Abstract

Purpose

This study examined the inter- and intra-patient variability in pharmacokinetics of AA and its metabolites abiraterone and Δ(4)-abiraterone (D4A), and potential contributing factors.

Methods

AA administered daily for ≥4 weeks concurrently with androgen deprivation therapy (ADT) for mCRPC were included. Pharmacokinetic evaluation was performed at two consecutive visits at least 4 weeks apart. Plasma samples were collected 24 h after last dose of AA to obtain drug trough level (DTL) of two active metabolites, abiraterone and D4A.

Results

39 plasma samples were obtained from 22 patients, with 17 patients had repeat DTL measurement. Considerable inter-patient variability in DTL was seen, with initial DTL for abiraterone ranging between 1.5 and 25.4 ng/ml (CV 61%) and for D4A between 0.2 and 2.5 ng/ml (CV 61%). Intra-patient variability in DTL for abiraterone varied between 0.85 and 336% and for D4A between 1.14 and 199%. There was no increase in AA exposure with use of dexamethasone (n = 5; DTL 13.9) compared with prednisone (n = 17; DTL 11.0 p = 0.5), dosing in fasted state (n = 13, DTL 12.1) compared to dosing in fed state (n = 9; DTL 11.1, p = 0.8), or chemotherapy-exposed (n = 10; DTL 8.9) compared to chemotherapy naïve (n = 12; DTL 14.0, p = 0.1).

Conclusions

Our cohort demonstrated high inter- and intra-patient variability in both abiraterone and D4A with fixed dosing of AA, with no effect from choice of corticosteroids, prior use of chemotherapy, or dosing in fasting state. Monitoring DTL of AA may be necessary to minimise risk of patients being under-dosed and earlier development of resistance.

Keywords

Abiraterone D4A Pharmacokinetics Prostate cancer 

Notes

Acknowledgements

MPM and HG acknowledge research support from Cancer Institute NSW research equipment grant scheme. AB acknowledges research scholar support from Sydney Vital Translational Cancer Research Centre.

Compliance with ethical standards

Conflict of interest

HG reports personal fees from BMS, personal fees from MSD, personal fees from Roche, grants and personal fees from Pfizer, and personal fees from Astra Zeneca, outside the submitted work. The remaining authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medical OncologyGosford HospitalSydneyAustralia
  2. 2.Kolling InstituteThe University of Sydney, Royal North Shore HospitalSydneyAustralia
  3. 3.Department of Medical OncologyThe Kinghorn Cancer CentreSydneyAustralia
  4. 4.Department of Molecular SciencesMacquarie UniversitySydneyAustralia
  5. 5.Department of Medical OncologyCrown Princess Mary Cancer Centre, Westmead HospitalSydneyAustralia
  6. 6.Macquarie University ClinicMacquarie University HospitalSydneyAustralia
  7. 7.Gosford HospitalGosfordAustralia

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