alexa P-glycoprotein restricts the penetration of oseltamivir across the blood-brain barrier.
Microbiology

Microbiology

Clinical Microbiology: Open Access

Author(s): Ose A, Kusuhara H, Yamatsugu K, Kanai M, Shibasaki M,

Abstract Share this page

Abstract Oseltamivir is an ethyl ester prodrug of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), the anti-influenza drug. Abnormal behavior has been suspected to be associated with oseltamivir medication in Japan. The purpose of the present study is to examine the involvement of transporters in the brain distribution of oseltamivir and its active form Ro 64-0802 across the blood-brain barrier (BBB). The brain-to-plasma concentration ratio (K(p,brain)) of oseltamivir after i.v. infusion of oseltamivir in FVB mice was increased by pretreatment with N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), a dual inhibitor for P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), whereas that of Ro 64-0802 was only slightly increased. Furthermore, the distribution volume of Ro 64-0802 following i.v. administration of Ro 64-0802 in the brain was similar to the capillary volume, suggesting its minimal distribution. The K(p,brain) value of oseltamivir in multidrug-resistant (Mdr) 1a/1b P-gp knockout mice was 5.5-fold higher than that in wild-type mice and comparable with that obtained by pretreatment with GF120918, whereas it was unchanged in Bcrp knockout mice. The K(p,brain) value of oseltamivir was significantly higher in newborn rats, which is in good agreement with the ontogenetic expression profile of P-gp. Intracellular accumulation of oseltamivir was lower in human and mouse P-gp-expressing cells, which was reversed by P-gp inhibitor valspodar (PSC833). These results suggest that P-gp limits the brain uptake of oseltamivir at the BBB and that Ro 64-0802 itself barely crosses the BBB. However, it may be possible that Ro 64-0802 is formed in the brain from the oseltamivir, considering the presence of carboxylesterase in the brain endothelial cells. This article was published in Drug Metab Dispos and referenced in Clinical Microbiology: Open Access

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 & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

eng[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

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