title: 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.
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne, UK. ruth.plummer@ncl.ac.uk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Plummer
authors.affiliation: Therakin Consulting, Sandbach, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Swaisland
authors.affiliation: UZ Leuven, Leuven, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Leunen
authors.affiliation: Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
authors.affiliation: CHU Sart-Tilman, Liege, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Jerusalem
authors.affiliation: Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: De Grève
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: Lolkema
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Patricia
authors.initials: P
authors.lastname: Soetekouw
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Mau-Sørensen
authors.affiliation: Herlev Hospital, Herlev, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Nielsen
authors.affiliation: King's College London at Guy's Hospital, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Spicer
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Anitra
authors.initials: A
authors.lastname: Fielding
authors.affiliation: AstraZeneca, Macclesfield, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: So
authors.affiliation: PHASTAR, London, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Bannister
authors.affiliation: Drug Development Unit, The Royal Marsden/Institute of Cancer Research, Sutton, UK.
authors.forename: L Rhoda
authors.initials: LR
authors.lastname: Molife
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D059305:Diet, High-Fat / Q000009:adverse effects; D004334:Drug Administration Schedule; D018565:Food-Drug Interactions; D006207:Half-Life; D007408:Intestinal Absorption; D008657:Metabolic Clearance Rate; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D010793:Phthalazines / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013607:Tablets
chemical_list: D000970:Antineoplastic Agents; C531550:olaparib; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013607:Tablets
keywords: Food effect; Olaparib; PARP inhibition; PK; Tablet