A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease

Nintedanib; Drug Interactions; Systemic Sclerosis

Detalles Bibliográficos
Autores: Vonk, Madelon, Guillen Del Castillo, Alfredo, Kreuter, Michael, Avis, Mandy, Marzin, Kristell, Mack, Salome R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/7807
Acceso en línea:https://hdl.handle.net/11351/7807
http://hdl.handle.net/11351/7807
Access Level:acceso abierto
Palabra clave:Pulmons - Malalties - Complicacions
Farmacocinètica
Esclerosi sistemàtica progressiva
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
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oai_identifier_str oai:recercat.cat:11351/7807
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
title A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
spellingShingle A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
Vonk, Madelon
Pulmons - Malalties - Complicacions
Farmacocinètica
Esclerosi sistemàtica progressiva
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
title_short A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
title_full A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
title_fullStr A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
title_full_unstemmed A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
title_sort A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
dc.creator.none.fl_str_mv Vonk, Madelon
Guillen Del Castillo, Alfredo
Kreuter, Michael
Avis, Mandy
Marzin, Kristell
Mack, Salome R.
author Vonk, Madelon
author_facet Vonk, Madelon
Guillen Del Castillo, Alfredo
Kreuter, Michael
Avis, Mandy
Marzin, Kristell
Mack, Salome R.
author_role author
author2 Guillen Del Castillo, Alfredo
Kreuter, Michael
Avis, Mandy
Marzin, Kristell
Mack, Salome R.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Vonk MC] Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. [Guillén-Del-Castillo A] Unitat de Malalties Autoimmunes Sistèmiques, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Kreuter M] Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany. [Avis M] Boehringer Ingelheim B.V., Alkmaar, The Netherlands. [Marzin K, Mack SR] Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Pulmons - Malalties - Complicacions
Farmacocinètica
Esclerosi sistemàtica progressiva
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
topic Pulmons - Malalties - Complicacions
Farmacocinètica
Esclerosi sistemàtica progressiva
DISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic
ENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica
description Nintedanib; Drug Interactions; Systemic Sclerosis
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/7807
http://hdl.handle.net/11351/7807
url https://hdl.handle.net/11351/7807
http://hdl.handle.net/11351/7807
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv European Journal of Drug Metabolism and Pharmacokinetics;47
https://doi.org/10.1007/s13318-021-00728-7
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414184594178048
spelling A Drug–Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung DiseaseVonk, MadelonGuillen Del Castillo, AlfredoKreuter, MichaelAvis, MandyMarzin, KristellMack, Salome R.Pulmons - Malalties - ComplicacionsFarmacocinèticaEsclerosi sistemàtica progressivaDISEASES::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, SystemicENFERMEDADES::enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémicaNintedanib; Drug Interactions; Systemic SclerosisNintedanib; Interacciones medicamentosas; Esclerosis sistémicaNintedanib; Interaccions farmacològiques; Esclerosi sistèmicaBackground and Objectives Nintedanib is a tyrosine kinase inhibitor approved for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD), idiopathic pulmonary fibrosis, and other chronic fibrosing ILDs with a progressive phenotype. As nintedanib may cause foetal harm, patients taking nintedanib should avoid pregnancy. The objective of this study was to investigate the effect of nintedanib co-administration on the pharmacokinetics of Microgynon (ethinylestradiol and levonorgestrel) in female patients with SSc-ILD. Methods This was an open-label, two-period, fixed-sequence, drug–drug interaction study. Female patients with SSc and ≥ 10% extent of fibrotic ILD on a high-resolution computed tomography scan were eligible to participate. In Period 1, patients received one Microgynon tablet (ethinylestradiol 30 μg and levonorgestrel 150 μg) ≥ 3 days before the first administration of nintedanib in Period 2. In Period 2, patients received one Microgynon tablet following intake of nintedanib 150 mg twice daily for ≥ 10 consecutive days. The primary pharmacokinetic endpoints were the areas under the plasma concentration–time curve of ethinylestradiol and levonorgestrel over the time interval from 0 to the last quantifiable data point (AUC0–tz) and the maximum measured concentrations of ethinylestradiol and levonorgestrel in plasma (Cmax). The secondary pharmacokinetic endpoint was the area under the plasma concentration–time curve of ethinylestradiol and levonorgestrel over the time interval from 0 extrapolated to infinity (AUC0–∞). The relative exposures of ethinylestradiol and levonorgestrel when administered alone and in combination with nintedanib were assessed using an ANOVA model. Results Seventeen patients were treated. Pharmacokinetic data from 15 patients were analysed. Plasma concentration–time profiles of ethinylestradiol and levonorgestrel were similar following administration of Microgynon before and after administration of nintedanib for ≥ 10 consecutive days. Adjusted geometric mean (gMean) ratios [90% confidence intervals (CIs)] for AUC0‒tz (101.4% [92.8, 110.7]) and AUC0‒∞ (101.2% [94.0, 109.1]) indicated that there was no difference in total ethinylestradiol exposure when Microgynon was administered before or after administration of nintedanib. The adjusted gMean ratio for Cmax of ethinylestradiol (116.7% [90% CI 107.6, 126.5]) indicated an increase in peak exposure in the presence of nintedanib. Adjusted gMean ratios [90% CIs] for AUC0-tz (96.4% [91.5, 101.6]) and Cmax (100.9% [89.9, 113.2]) indicated that there was no difference in total or peak levonorgestrel exposure when Microgynon was administered before or after administration of nintedanib. The adjusted gMean ratio for AUC0‒∞ of levonorgestrel indicated a decrease in total exposure in the presence of nintedanib (88.1% [90% CI 80.0, 97.0]). Conclusion Pharmacokinetic data indicate that there is no relevant effect of nintedanib on plasma exposure to ethinylestradiol and levonorgestrel in female patients with SSc-ILD.SpringerInstitut Català de la Salut[Vonk MC] Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands. [Guillén-Del-Castillo A] Unitat de Malalties Autoimmunes Sistèmiques, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Kreuter M] Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany. [Avis M] Boehringer Ingelheim B.V., Alkmaar, The Netherlands. [Marzin K, Mack SR] Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, GermanyVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/7807http://hdl.handle.net/11351/7807Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésEuropean Journal of Drug Metabolism and Pharmacokinetics;47https://doi.org/10.1007/s13318-021-00728-7Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/78072026-05-29T05:05:01Z
score 15.81155

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