Bridging Olaparib Capsule and Tablet Formulations Using Population Pharmacokinetic Meta-analysis in Oncology Patients.
Antineoplastic Agents
/ administration & dosage
Biological Availability
Capsules
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Female
Humans
Models, Biological
Ovarian Neoplasms
/ blood
Phthalazines
/ administration & dosage
Piperazines
/ administration & dosage
Tablets
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
pubmed:
26
10
2018
medline:
9
7
2020
entrez:
26
10
2018
Statut:
ppublish
Résumé
Olaparib is a first-in-class potent oral poly(ADP-ribose) polymerase inhibitor. The aims of this analysis were to establish an integrated population pharmacokinetic (PK) model of olaparib in patients with solid tumors and to bridge the PK of olaparib between capsule and tablet formulations. The population PK model was developed using plasma concentration data from 659 patients in 11 phase I, II, and III studies of olaparib tablets/capsules monotherapy. Relative bioavailability between the tablet and capsule formulations was estimated and the relative exposure between olaparib tablet and capsule therapeutic doses was further assessed. The concentration-time profile was described using a two-compartment model with sequential zero- and first-order absorption and first-order elimination for both capsules and tablets with different absorption parameters. Multiple-dose clearance compared with single-dose clearance was reduced by approximately 15% (auto-inhibition). Disease severity had an impact on olaparib clearance, and tablet strength had an impact on K This analysis bridged the olaparib capsule and tablet formulation PK and provided key assessment to support the approval of the olaparib tablet formulation in patients with ovarian cancer, regardless of their BRCA mutation status.
Sections du résumé
BACKGROUND
Olaparib is a first-in-class potent oral poly(ADP-ribose) polymerase inhibitor.
OBJECTIVES
The aims of this analysis were to establish an integrated population pharmacokinetic (PK) model of olaparib in patients with solid tumors and to bridge the PK of olaparib between capsule and tablet formulations.
METHODS
The population PK model was developed using plasma concentration data from 659 patients in 11 phase I, II, and III studies of olaparib tablets/capsules monotherapy. Relative bioavailability between the tablet and capsule formulations was estimated and the relative exposure between olaparib tablet and capsule therapeutic doses was further assessed.
RESULTS
The concentration-time profile was described using a two-compartment model with sequential zero- and first-order absorption and first-order elimination for both capsules and tablets with different absorption parameters. Multiple-dose clearance compared with single-dose clearance was reduced by approximately 15% (auto-inhibition). Disease severity had an impact on olaparib clearance, and tablet strength had an impact on K
CONCLUSION
This analysis bridged the olaparib capsule and tablet formulation PK and provided key assessment to support the approval of the olaparib tablet formulation in patients with ovarian cancer, regardless of their BRCA mutation status.
Identifiants
pubmed: 30357650
doi: 10.1007/s40262-018-0714-x
pii: 10.1007/s40262-018-0714-x
doi:
Substances chimiques
Antineoplastic Agents
0
Capsules
0
Phthalazines
0
Piperazines
0
Tablets
0
olaparib
WOH1JD9AR8
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
615-625Références
Comput Methods Programs Biomed. 2005 Sep;79(3):241-57
pubmed: 16023764
Clin Cancer Res. 2009 Apr 1;15(7):2497-506
pubmed: 19258444
N Engl J Med. 2009 Jul 9;361(2):123-34
pubmed: 19553641
AAPS J. 2009 Sep;11(3):558-69
pubmed: 19649712
Lancet. 2010 Jul 24;376(9737):235-44
pubmed: 20609467
Lancet. 2010 Jul 24;376(9737):245-51
pubmed: 20609468
AAPS J. 2011 Jun;13(2):143-51
pubmed: 21302010
Cancer Sci. 2012 Mar;103(3):504-9
pubmed: 22145984
J Clin Oncol. 2012 Feb 1;30(4):372-9
pubmed: 22203755
N Engl J Med. 2012 Apr 12;366(15):1382-92
pubmed: 22452356
Adv Ther. 2015 Jun;32(6):510-22
pubmed: 26048134
Cancer Chemother Pharmacol. 2015 Oct;76(4):723-9
pubmed: 26242220
N Engl J Med. 2015 Oct 29;373(18):1697-708
pubmed: 26510020
Mol Cell. 2015 Nov 19;60(4):547-60
pubmed: 26590714
Target Oncol. 2016 Jun;11(3):401-15
pubmed: 27169564
Cancer Chemother Pharmacol. 2016 Sep;78(3):525-31
pubmed: 27422301
J Clin Pharmacol. 2017 Mar;57(3):336-344
pubmed: 27530649
Clin Ther. 2016 Oct;38(10):2286-2299
pubmed: 27745744
Cancer Chemother Pharmacol. 2017 Jul;80(1):165-175
pubmed: 28577239
Xenobiotica. 2018 Jun;48(6):555-564
pubmed: 28657402
Lancet Oncol. 2017 Sep;18(9):1274-1284
pubmed: 28754483