| Regional P-glycoprotein activity and inhibition at the human blood-brain barrier as imaged by positron emission tomography. | |
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MedLine Citation:
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PMID: 20336065 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We used positron emission tomography (PET) to evaluate the contribution of P-glycoprotein (P-gp), present at the human blood-brain barrier (BBB), to regional drug distribution in the brain. Eleven healthy volunteers underwent PET imaging with [(11)C]-verapamil before and during cyclosporine A infusion. Regional P-gp inhibition was expressed as cyclosporine A-induced percentage change in the distributional clearance of verapamil (K(1)) in the brain, normalized to the regional blood flow (rCBF). K(1) estimates were similar across gray-matter regions of the brain and lower in the white matter regions, but all these estimates were considerably lower than rCBF. Normalization of K(1) by rCBF diminished the differences in estimates related to gray matter and white matter. In contrast, the K(1) for the pituitary, which is situated outside the BBB, approximated the rCBF. The magnitude of P-gp inhibition was comparable across BBB-protected brain structures. Our results indicate that P-gp and its inhibition equally affect the distribution of drugs (and therefore their neuro-efficacy and toxicity) in the various brain regions protected by the BBB. |
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Authors:
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S Eyal; B Ke; M Muzi; J M Link; D A Mankoff; A C Collier; J D Unadkat |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2010-03-24 |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: 87 ISSN: 1532-6535 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-21 Completed Date: 2010-05-03 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 579-85 Citation Subset: AIM; IM |
Affiliation:
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Department of Pharmaceutics, University of Washington, Seattle, Washington, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blood-Brain Barrier / drug effects*, radionuclide imaging* Brain / drug effects, metabolism, radionuclide imaging* Cyclosporine / metabolism, pharmacology Female Humans Male Middle Aged P-Glycoprotein / antagonists & inhibitors*, genetics, metabolism* Positron-Emission Tomography / methods* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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R33 AG031485/AG/NIA NIH HHS; R33 AG031485-01/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ABCB1 protein, human; 0/P-Glycoprotein; 59865-13-3/Cyclosporine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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