Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors: Results of Two Phase I Open-label Studies
作者: Luc DirixHelen SwaislandHenk M.W. VerheulSylvie RotteyKarin LeunenGuy JerusalemChristian RolfoDorte NielsenL. Rhoda MolifeRebecca KristeleitJudith de Vos-GeelenMorten Mau-SørensenPatricia SoetekouwCarla van HerpenAnitra FieldingKaren SoWendy BannisterRuth Plummer
作者单位: 1Medical Oncology, Sint-Augustinus-University of Antwerp, Antwerp, Belgium
2AstraZeneca, Macclesfield, United Kingdom
3Department of Medical Oncology, VU Medisch Centrum, Amsterdam, the Netherlands
4Department of Medical Oncology, Ghent University Hospital and Heymans Institute of Pharmacology, Ghent, Belgium
5Universitair Ziekenhuizen Leuven, Leuven, Belgium
6CHU Sart-Tilman and Liege University, Liege, Belgium
7Oncology Department, Universitair Ziekenhuis Antwerpen, Antwerp, Belgium
8Department of Oncology, Herlev and Gentofte Hospital, Herlev, Denmark
9The Royal Marsden and Institute of Cancer Research, Sutton, United Kingdom
10University College London Cancer Institute, London, United Kingdom
11Division of Medical Oncology, Maastricht University Medical Center, Maastricht, the Netherlands
12Department of Oncology, University Hospital, Rigshospitalet, Copenhagen, Denmark
13Radboud University Medical Center, Nijmegen, the Netherlands
14AstraZeneca, Cambridge, United Kingdom
15PHASTAR, London, United Kingdom
16Northern Centre for Cancer Care, Newcastle upon Tyne, United Kingdom
刊名: Clinical Therapeutics, 2016, Vol.38 (10), pp.2286-2299
来源数据库: Elsevier Journal
DOI: 10.1016/j.clinthera.2016.08.010
关键词: CYP3A4itraconazoleolaparibpharmacokineticrifampin
原始语种摘要: Abstract(#br)Purpose(#br)The metabolism of olaparib, a potent inhibitor of poly(ADP-ribose) polymerase (PARP) with demonstrated efficacy in patients with BRCA -mutated ovarian cancer, is mediated by cytochrome P450 (CYP) enzymes (predominantly CYP3A4/5). We assessed the potential of a CYP3A4 inhibitor (itraconazole) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses.(#br)Methods(#br)Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors. In Study 7, patients received olaparib alone and co-administered with itraconazole; in Study 8, a separate group of patients received olaparib alone and co-administered with rifampin. No interaction between itraconazole and olaparib was concluded if...
全文获取路径: Elsevier  (合作)
影响因子:2.23 (2012)