Full metadata record
DC Field | Value | Language |
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dc.creator | Jong, J. (Jan) de | - |
dc.creator | Mitselos, A. (Anna) | - |
dc.creator | Jurczak, W. (Wojciech) | - |
dc.creator | Cordoba, R. (Raul) | - |
dc.creator | Panizo, C. (Carlos) | - |
dc.creator | Wrobel, T. (Tomasz) | - |
dc.creator | Dlugosz-Danecka, M. (Monika) | - |
dc.creator | Jiao, J. (James) | - |
dc.creator | Sukbuntherng, J. (Juthamas) | - |
dc.creator | Ouellet, D. (Daniele) | - |
dc.creator | Hellemans, P. (Peter) | - |
dc.date.accessioned | 2023-05-23T08:18:35Z | - |
dc.date.available | 2023-05-23T08:18:35Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | de-Jong, J. (Jan); Mitselos, A. (Anna); Jurczak, W. (Wojciech); et al. "Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6". Pharmacology Research and Perspectives. 8 (5), 2020, | es |
dc.identifier.issn | 2052-1707 | - |
dc.identifier.uri | https://hdl.handle.net/10171/66333 | - |
dc.description.abstract | Ibrutinib may inhibitintestinal CYP3A4 and induce CYP2B6 and/or CYP3A. Secondary to potential induction, ibrutinib may reduce the exposure and effectiveness of oral contraceptives (OCs). This phase I study evaluated the effect of ibrutinib on the pharmacokinetics of the CYP2B6 substrate bupropion, CYP3A substrate midazolam, and OCs ethinylestradiol (EE) and levonorgestrel (LN). Female patients (N = 22) with B-cell malignancies received single doses of EE/LN (30/150 μg) and bupropion/midazolam (75/2 mg) during a pretreatment phase on days 1 and 3, respectively (before starting ibrutinib on day 8), and again after ibrutinib 560 mg/day for ≥ 2 weeks. Intestinal CYP3A inhibition was assessed on day 8 (single-dose ibrutinib plus single-dose midazolam). Systemic induction was assessed at steady-state on days 22 (EE/LN plus ibrutinib) and 24 (bupropion/midazolam plus ibrutinib). The geometric mean ratios (GMRs; test/reference) for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were derived using linear mixed-effects models (90% confidence interval within 80%-125% indicated no interaction). On day 8, the GMR for midazolam exposure with ibrutinib coadministration was ≤ 20% lower than the reference, indicating lack of intestinal CYP3A4 inhibition. At ibrutinib steady-state, the Cmax and AUC of EE were 33% higher than the reference, which was not considered clinically relevant. No substantial changes were noted for LN, midazolam, or bupropion. No unexpected safety findings were observed. A single dose of ibrutinib did not inhibit intestinal CYP3A4, and repeated administration did not induce CYP3A4/2B6, as assessed using EE, LN, midazolam, and bupropion. | es_ES |
dc.description.sponsorship | Janssen Global Services, LLC | es_ES |
dc.language.iso | eng | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Cytochrome P450 | es_ES |
dc.subject | Drug interactions | es_ES |
dc.subject | Pharmacokinetics | es_ES |
dc.subject | Phase I | es_ES |
dc.title | Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.description.note | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 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. | es_ES |
dc.identifier.doi | 10.1002/prp2.649 | - |
dadun.citation.number | 5 | es_ES |
dadun.citation.publicationName | Pharmacology Research and Perspectives | es_ES |
dadun.citation.volume | 8 | es_ES |
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