OATP1A/1B, CYP3A, ABCB1, and ABCG2 limit oral availability of the NTRK inhibitor larotrectinib, while ABCB1 and ABCG2 also restrict its brain accumulation.

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Abstract

Larotrectinib is a FDA-approved oral small-molecule inhibitor for treatment of neurotrophic tropomyosin receptor kinase fusion-positive cancer. We here investigated the functions of the multidrug efflux transporters ABCB1 and ABCG2, the SLCO1A/1B (OATP1A/1B) uptake transporters, and the multispecific drug-metabolizing enzyme CYP3A in larotrectinib pharmacokinetic behaviour.

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Journal

Journal ID (iso-abbrev): Br J Pharmacol

Title: British journal of pharmacology

Publisher: Wiley

ISSN (Electronic): 1476-5381

ISSN (Print): 0007-1188

Publication date (Electronic): Jul 2020

Volume: 177

Issue: 13

Affiliations

[1 ] Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

[2 ] Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacology, Utrecht University, Utrecht, The Netherlands.

[3 ] Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Article

DOI: 10.1111/bph.15034

PMC ID: 7279963

PubMed ID: 32087611

SO-VID: 188ef684-48f3-46fd-bd8f-f43a54c83648

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