Cargando…
Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor
This phase I study (CO‐338‐044; NCT02740712), conducted in patients with advanced solid tumors, evaluated the effect of the poly(ADP‐ribose) polymerase (PARP) inhibitor rucaparib on the pharmacokinetics (PK) of caffeine 200 mg, warfarin 10 mg, omeprazole 40 mg, and midazolam 2 mg (cytochrome P450 (C...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342242/ https://www.ncbi.nlm.nih.gov/pubmed/30427584 http://dx.doi.org/10.1111/cts.12600 |
_version_ | 1783389097335717888 |
---|---|
author | Xiao, Jim J. Nowak, Dorota Ramlau, Rodryg Tomaszewska‐Kiecana, Monika Wysocki, Piotr J. Isaacson, Jeff Beltman, Jeri Nash, Eileen Kaczanowski, Robert Arold, Gerhard Watkins, Simon |
author_facet | Xiao, Jim J. Nowak, Dorota Ramlau, Rodryg Tomaszewska‐Kiecana, Monika Wysocki, Piotr J. Isaacson, Jeff Beltman, Jeri Nash, Eileen Kaczanowski, Robert Arold, Gerhard Watkins, Simon |
author_sort | Xiao, Jim J. |
collection | PubMed |
description | This phase I study (CO‐338‐044; NCT02740712), conducted in patients with advanced solid tumors, evaluated the effect of the poly(ADP‐ribose) polymerase (PARP) inhibitor rucaparib on the pharmacokinetics (PK) of caffeine 200 mg, warfarin 10 mg, omeprazole 40 mg, and midazolam 2 mg (cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, and CYP3A substrates; dosed as a cocktail) and digoxin 0.25 mg (P‐glycoprotein (P‐gp) substrate; dosed separately) without rucaparib and following oral rucaparib 600 mg b.i.d. Geometric mean (GM) ratios (90% confidence interval (CI)) of area under the concentration‐time curve (AUC) from time zero to last quantifiable measurement with and without rucaparib were: caffeine, 2.26 (1.93–2.65); S‐warfarin, 1.49 (1.40–1.58); omeprazole, 1.55 (1.32–1.83); midazolam, 1.39 (1.14–1.68); and digoxin, 1.20 (1.12–1.29). There was limited effect on peak concentration of the substrates (GM ratios, 0.99–1.13). At steady state, rucaparib 600 mg b.i.d. moderately inhibited CYP1A2, weakly inhibited CYP2C9, CYP2C19, and CYP3A, and marginally increased digoxin exposure. |
format | Online Article Text |
id | pubmed-6342242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63422422019-01-24 Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor Xiao, Jim J. Nowak, Dorota Ramlau, Rodryg Tomaszewska‐Kiecana, Monika Wysocki, Piotr J. Isaacson, Jeff Beltman, Jeri Nash, Eileen Kaczanowski, Robert Arold, Gerhard Watkins, Simon Clin Transl Sci Research This phase I study (CO‐338‐044; NCT02740712), conducted in patients with advanced solid tumors, evaluated the effect of the poly(ADP‐ribose) polymerase (PARP) inhibitor rucaparib on the pharmacokinetics (PK) of caffeine 200 mg, warfarin 10 mg, omeprazole 40 mg, and midazolam 2 mg (cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, and CYP3A substrates; dosed as a cocktail) and digoxin 0.25 mg (P‐glycoprotein (P‐gp) substrate; dosed separately) without rucaparib and following oral rucaparib 600 mg b.i.d. Geometric mean (GM) ratios (90% confidence interval (CI)) of area under the concentration‐time curve (AUC) from time zero to last quantifiable measurement with and without rucaparib were: caffeine, 2.26 (1.93–2.65); S‐warfarin, 1.49 (1.40–1.58); omeprazole, 1.55 (1.32–1.83); midazolam, 1.39 (1.14–1.68); and digoxin, 1.20 (1.12–1.29). There was limited effect on peak concentration of the substrates (GM ratios, 0.99–1.13). At steady state, rucaparib 600 mg b.i.d. moderately inhibited CYP1A2, weakly inhibited CYP2C9, CYP2C19, and CYP3A, and marginally increased digoxin exposure. John Wiley and Sons Inc. 2018-12-20 2019-01 /pmc/articles/PMC6342242/ /pubmed/30427584 http://dx.doi.org/10.1111/cts.12600 Text en © 2018 Clovis Oncology Inc. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Xiao, Jim J. Nowak, Dorota Ramlau, Rodryg Tomaszewska‐Kiecana, Monika Wysocki, Piotr J. Isaacson, Jeff Beltman, Jeri Nash, Eileen Kaczanowski, Robert Arold, Gerhard Watkins, Simon Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor |
title | Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor |
title_full | Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor |
title_fullStr | Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor |
title_full_unstemmed | Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor |
title_short | Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor |
title_sort | evaluation of drug–drug interactions of rucaparib and cyp1a2, cyp2c9, cyp2c19, cyp3a, and p‐gp substrates in patients with an advanced solid tumor |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342242/ https://www.ncbi.nlm.nih.gov/pubmed/30427584 http://dx.doi.org/10.1111/cts.12600 |
work_keys_str_mv | AT xiaojimj evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT nowakdorota evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT ramlaurodryg evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT tomaszewskakiecanamonika evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT wysockipiotrj evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT isaacsonjeff evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT beltmanjeri evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT nasheileen evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT kaczanowskirobert evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT aroldgerhard evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor AT watkinssimon evaluationofdrugdruginteractionsofrucaparibandcyp1a2cyp2c9cyp2c19cyp3aandpgpsubstratesinpatientswithanadvancedsolidtumor |