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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2017

01-07-2017 | Original Article

Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women’s cancers

Authors: Cody J. Peer, Jung-Min Lee, Jeffrey Roth, Louis Rodgers, Jeffers Nguyen, Christina M. Annunziata, Lori Minasian, Elise C. Kohn, William D. Figg

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2017

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Abstract

Purpose

Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance.

Methods

To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters.

Results

Clearance (6.8 L/h) and volume (33 L) estimates were comparable with literature. The only significant covariate was the presence of carboplatin on olaparib clearance, consistent with published noncompartmental PK and in vitro data.

Conclusions

Simulations predicted lower steady-state peak/trough olaparib exposure through 24–36 h post carboplatin pre-treatment, but this effect was lost by day 2 and thus no dose adjustment is recommended.
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Metadata
Title
Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women’s cancers
Authors
Cody J. Peer
Jung-Min Lee
Jeffrey Roth
Louis Rodgers
Jeffers Nguyen
Christina M. Annunziata
Lori Minasian
Elise C. Kohn
William D. Figg
Publication date
01-07-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3346-1

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