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dc.creatorJong, J. (Jan) de-
dc.creatorMitselos, A. (Anna)-
dc.creatorJurczak, W. (Wojciech)-
dc.creatorCordoba, R. (Raul)-
dc.creatorPanizo, C. (Carlos)-
dc.creatorWrobel, T. (Tomasz)-
dc.creatorDlugosz-Danecka, M. (Monika)-
dc.creatorJiao, J. (James)-
dc.creatorSukbuntherng, J. (Juthamas)-
dc.creatorOuellet, D. (Daniele)-
dc.creatorHellemans, P. (Peter)-
dc.identifier.citationde-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.description.abstractIbrutinib 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.sponsorshipJanssen Global Services, LLCes_ES
dc.subjectCytochrome P450es_ES
dc.subjectDrug interactionses_ES
dc.subjectPhase Ies_ES
dc.titleIbrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6es_ES
dc.description.noteThis 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
dadun.citation.publicationNamePharmacology Research and Perspectiveses_ES

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