dc.contributor
Institut Català de la Salut
dc.contributor
[Chen J] Pfzer, New York, NY, USA. Genentech, South San Francisco, CA, USA. [Bearz A] National Cancer Institute, Aviano, Italy. [Kim DW] Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea. [Mamdani H] Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. [Bauman J] Fox Chase Cancer Center, Philadelphia, PA, USA. [Chiari R] Medical Oncology, AULSS6 Veneto, Padua, Italy. [Felip E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Chen, Joseph
dc.contributor.author
bearz, alessandra
dc.contributor.author
Kim, Dong-Wan
dc.contributor.author
Mamdani, Hirva
dc.contributor.author
Bauman, J. R.
dc.contributor.author
chiari, rita
dc.contributor.author
FELIP, ENRIQUETA
dc.date.accessioned
2025-10-24T09:34:05Z
dc.date.available
2025-10-24T09:34:05Z
dc.date.issued
2024-02-13T10:46:23Z
dc.date.issued
2024-02-13T10:46:23Z
dc.identifier
Chen J, Bearz A, Dong-Wan K, Mamdani H, Bauman J, Chiari R, et al. Evaluation of the Effect of Lorlatinib on CYP2B6, CYP2C9, UGT, and P-Glycoprotein Substrates in Patients with Advanced Non-Small Cell Lung Cancer. Clin Pharmacokinet. 2024 Feb;63:171–182.
dc.identifier
https://hdl.handle.net/11351/11032
dc.identifier
10.1007/s40262-023-01309-4
dc.identifier
001121084900001
dc.identifier.uri
http://hdl.handle.net/11351/11032
dc.description.abstract
Lorlatinib; Glycoprotein; Advanced non-small cell lung cancer
dc.description.abstract
Lorlatinib; Glicoproteïna; Càncer de pulmó de cèl·lules no petites
dc.description.abstract
Lorlatinib; Glicoproteína; Cáncer de pulmón de células no pequeñas
dc.description.abstract
Background and Objective
Lorlatinib is a tyrosine kinase inhibitor approved for the treatment of advanced anaplastic lymphoma kinase–positive non-small cell lung cancer. This study assessed the effect of steady-state lorlatinib on the metabolic enzymes cytochrome P450 (CYP) 2B6, CYP2C9, and uridine 5′-diphospho-glucuronosyltransferase (UGT) and the P-glycoprotein (P-gp) transporter.
Methods
Thirty-two patients received a single oral dose of a probe drug on Day − 2 to determine the pharmacokinetics of the probe drug alone. Starting on Day 1, patients received 100 mg oral lorlatinib daily. On Day 15, a single oral dose of the probe drug was administered concurrently with lorlatinib. Pharmacokinetic parameters for these probe substrates were assessed.
Results
Plasma exposures of all probe substrates were reduced by lorlatinib compared with the probe alone. The greatest reduction in area under the plasma concentration–time curve from time zero to infinity (AUC∞) and maximum (peak) plasma drug concentration (Cmax) (67% and 63% decrease, respectively) was observed with the P-gp probe substrate fexofenadine. Lorlatinib coadministration also decreased the AUC∞ and Cmax of bupropion (CYP2B6 probe substrate) by 25% and 27%, tolbutamide (CYP2C9 probe substrate) by 43% and 15%, and acetaminophen (UGT probe substrate) by 45% and 28%, respectively.
Conclusions
Lorlatinib is a net moderate inducer of P-gp and a weak inducer of CYP2B6, CYP2C9, and UGT after steady state is achieved with daily dosing. Medications that are P-gp substrates with a narrow therapeutic window should be avoided in patients taking lorlatinib; no dose modifications are needed with substrates of CYP2B6, CYP2C9, or UGT.
ClinicalTrials.gov: NCT01970865.
dc.description.abstract
This study was sponsored by Pfizer.
dc.format
application/pdf
dc.relation
Clinical Pharmacokinetics;63
dc.relation
https://doi.org/10.1007/s40262-023-01309-4
dc.rights
Attribution-NonCommercial 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Proteïnes quinases - Inhibidors - Ús terapèutic
dc.subject
Pulmons - Càncer - Tractament
dc.subject
Glicoproteïnes
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins
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CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::glicoproteínas
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas
dc.title
Evaluation of the Effect of Lorlatinib on CYP2B6, CYP2C9, UGT, and P-Glycoprotein Substrates in Patients with Advanced Non-Small Cell Lung Cancer
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
