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Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours.

Abstract：

BACKGROUND:The oral PARP inhibitor olaparib has shown efficacy in patients with BRCA-mutated cancer. This Phase I, open-label, three-part study (Parts A-C) in patients with advanced solid tumours evaluated the effect of food on the pharmacokinetics (PK) of olaparib when administered in tablet formulation. METHODS:PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part C, patients were allowed continued access to olaparib. Safety was assessed throughout, with data reported for Parts A and B. RESULTS:A total of 60 and 56 patients were evaluable for safety and PK analyses, respectively; 57 patients entered Part B. Rate of olaparib absorption was slower in the presence of food (t max delayed by 2.5 h), resulting in a statistically significant ~21 % decrease in peak plasma exposure (C max) [ratio of geometric means (90 % CI), 0.79 (0.72, 0.86)] but only a marginal increase in olaparib absorption (AUC0-∞) [ratio of geometric means (90 % CI), 1.08 (1.01, 1.16)]. The point estimate and 90 % CI for the AUC0-∞ treatment ratio were within pre-defined bioequivalence limits (0.80-1.25). Adverse event data were consistent with the known safety profile of olaparib. CONCLUSIONS:Results of this study showed that a high-fat meal decreases the rate of absorption and peak exposure to olaparib 300 mg tablets, although in the absence of an effect on the extent of olaparib absorption.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Plummer R,Swaisland H,Leunen K,van Herpen CM,Jerusalem G,De Grève J,Lolkema MP,Soetekouw P,Mau-Sørensen M,Nielsen D,Spicer J,Fielding A,So K,Bannister W,Molife LR

doi

10.1007/s00280-015-2836-2

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

723-9

issue

eissn

0344-5704

issn

1432-0843

pii

10.1007/s00280-015-2836-2

journal_volume

pub_type

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Olaparib tablet formulation: effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours.