alexa Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors.
Pharmaceutical Sciences

Pharmaceutical Sciences

Clinical Pharmacology & Biopharmaceutics

Author(s): Khurana V, Minocha M, Pal D, Mitra AK

Abstract Share this page

Abstract BACKGROUND: The potential of tyrosine kinase inhibitors (TKIs) interacting with other therapeutics through hepatic uptake transporter inhibition has not been fully delineated in drug-drug interactions (DDIs). This study was designed to estimate the half-maximal inhibitory concentration (IC50) values of five small-molecule TKIs (pazopanib, nilotinib, vandetanib, canertinib and erlotinib) interacting with organic anion-transporting polypeptides (OATPs): OATP-1B1 and -1B3. METHODS: The IC50 values of TKIs and rifampicin (positive control) were determined by concentration-dependent inhibition of TKIs on cellular accumulation of radiolabeled probe substrates [3H]estrone sulfate and [3H]cholecystokinin octapeptide. Chinese hamster ovary cells transfected with humanized OATP-1B1 and OATP-1B3 transporter proteins, respectively, were utilized to carry out these studies. RESULTS: Pazopanib and nilotinib show inhibitory activity on OATP-1B1 transporter protein. IC50 values for rifampicin, pazopanib and nilotinib were 10.46±1.15, 3.89±1.21 and 2.78±1.13 μM, respectively, for OATP-1B1 transporter. Vandetanib, canertinib and erlotinib did not exhibit any inhibitory potency toward OATP-1B1 transporter protein. Only vandetanib expressed inhibitory potential toward OATP-1B3 transporter protein out of the five selected TKIs. IC50 values for rifampicin and vandetanib for OATP-1B3 transporter inhibition were 3.67±1.20 and 18.13±1.21 μM, respectively. No significant inhibition in the presence of increasing concentrations of pazopanib, nilotinib, canertinib and erlotinib were observed for OATP-1B3 transporter. CONCLUSIONS: Because selected TKIs are inhibitors of OATP-1B1 and -1B3 expressed in hepatic tissue, these compounds can be regarded as molecular targets for transporter-mediated DDIs. These findings provide the basis for further preclinical and clinical studies investigating the transporter-based DDI potential of TKIs.
This article was published in Drug Metabol Drug Interact and referenced in Clinical Pharmacology & Biopharmaceutics

Relevant Expert PPTs

Relevant Speaker PPTs

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords