| Title |
Effect of Food on the Pharmacokinetics of Olaparib after Oral Dosing of the Capsule Formulation in Patients with Advanced Solid Tumors
|
|---|---|
| Published in |
Advances in Therapy, June 2015
|
| DOI | 10.1007/s12325-015-0214-4 |
| Pubmed ID | |
| Authors |
Christian Rolfo, Helen Swaisland, Karin Leunen, Annemie Rutten, Patricia Soetekouw, Sarah Slater, Henk M. W. Verheul, Anitra Fielding, Karen So, Wendy Bannister, Emma Dean |
| Abstract |
The oral, potent poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, is well tolerated at doses of ≤400 mg twice daily (BID) (administered as capsules), and has shown efficacy in patients with advanced BRCA-mutated ovarian and breast cancer. This Phase I, open-label, randomized trial investigates the effect of food on the pharmacokinetics of olaparib in patients with refractory/resistant advanced solid tumors. In Part A, a three-period crossover study, patients received a single oral dose of olaparib 400 mg (8 × 50 mg capsules) in three prandial states: fasted, a high-fat meal or a standard meal (with a 5-14 day washout). Blood samples for pharmacokinetic (PK) assessments were taken pre-dose and up to 72 h post-dose. After completing Part A, patients could enter Part B, where they would receive olaparib 400 mg BID. 32 patients were randomized; 31 contributed to the PK statistical analysis and entered Part B. The presence of food slowed the rate of absorption (time to maximal plasma concentration [t max] was delayed by ~2 h). Maximum plasma concentration (C max) was increased by 10% following a standard meal and was unchanged with a high-fat meal (ratio of geometric means [90% confidence interval (CI)]: 1.10 [1.02-1.20] for standard and 1.00 [0.92-1.09] for high-fat meal). The extent of olaparib absorption (AUC) was increased by ~20% in the fed state (ratio of geometric means: 1.21 [1.10-1.33] for standard and 1.19 [1.08-1.31] for high-fat meal). The presence of food decreased the rate and increased the extent of absorption of olaparib following oral dosing of the capsule formulation. However, the effects of food on olaparib PK were not deemed clinically important, according to predefined criteria. Safety data were consistent with the known safety profile of olaparib. AstraZeneca. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 65 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 65 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 11 | 17% |
| Student > Bachelor | 8 | 12% |
| Other | 6 | 9% |
| Student > Ph. D. Student | 5 | 8% |
| Researcher | 4 | 6% |
| Other | 9 | 14% |
| Unknown | 22 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 22 | 34% |
| Biochemistry, Genetics and Molecular Biology | 5 | 8% |
| Nursing and Health Professions | 5 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 5% |
| Agricultural and Biological Sciences | 3 | 5% |
| Other | 2 | 3% |
| Unknown | 25 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 June 2015.
All research outputs
#18,414,796
of 22,811,321 outputs
Outputs from Advances in Therapy
#1,629
of 2,338 outputs
Outputs of similar age
#192,372
of 266,602 outputs
Outputs of similar age from Advances in Therapy
#18
of 23 outputs
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