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
| Autores: | , , , , , |
|---|---|
| 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 |
| id |
ES_9854d1cb39468f331db0700a6d1c4de1 |
|---|---|
| oai_identifier_str |
oai:recercat.cat:11351/7807 |
| network_acronym_str |
ES |
| network_name_str |
España |
| 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 Disease Vonk, Madelon Guillen Del Castillo, Alfredo Kreuter, Michael Avis, Mandy Marzin, Kristell Mack, Salome R. 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 Nintedanib; Drug Interactions; Systemic Sclerosis Nintedanib; Interacciones medicamentosas; Esclerosis sistémica Nintedanib; Interaccions farmacològiques; Esclerosi sistèmica Background 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. Springer https://hdl.handle.net/11351/7807 http://hdl.handle.net/11351/7807 |
| 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 |
| 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 |
| 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 |
| topic_facet |
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 |
| format |
article |
| status_str |
publishedVersion |
| url |
https://hdl.handle.net/11351/7807 http://hdl.handle.net/11351/7807 |
| eu_rights_str_mv |
openAccess |
| publisher |
Springer |
| institution |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| collection |
Recercat. Dipósit de la Recerca de Catalunya |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
| instname_str |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| _version_ |
1878438237747281920 |
| publishDateSort |
2022 |
| author_browse |
Avis, Mandy Guillen Del Castillo, Alfredo Kreuter, Michael Mack, Salome R. Marzin, Kristell Vonk, Madelon |
| publisherStr |
Springer |
| score |
6,9303427 |