| pubmed-article:15858856 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0040300 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0026809 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0006104 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0242643 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0525005 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0441889 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0314603 | lld:lifeskim |
| pubmed-article:15858856 | lifeskim:mentions | umls-concept:C0205464 | lld:lifeskim |
| pubmed-article:15858856 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:15858856 | pubmed:dateCreated | 2005-5-3 | lld:pubmed |
| pubmed-article:15858856 | pubmed:abstractText | Insufficient concentrations of protease inhibitors such as nelfinavir may reduce the effectiveness of HIV dementia treatment. The efflux transporter mdr1 product P-glycoprotein (P-gp) has been demonstrated to play a role in limiting nelfinavir brain levels. The goal of this study was to compare the effect of GF120918 (10 mg/kg, IV), a P-gp inhibitor, on intravenous nelfinavir (10 mg/kg) in vivo disposition and tissue penetration in P-gp-competent mdr1a/1b (+/+) mice versus P-gp double knockout mdr1a/1b (-/-) mice. Intravenous administration with the P-gp inhibitor GF120918 to mdr1a/1b (+/+) mice increased nelfinavir concentrations over a range of 2.3- to 27-fold, whereas nelfinavir distribution in mdr1a/1b (-/-) mice was 2- to 16-fold higher than that in their wild counterparts. Nelfinavir levels after GF120918 coadministration were higher in the heart, liver, and kidneys than those detected with mdr1a/1b knockout mice. In contrast, mdr1a/1b knockout mice exhibited higher nelfinavir levels in the brain (16.1-fold vs. 8.9-fold increase) and spleen (4.1-fold vs. 2.3-fold increase) compared to pharmacological inhibition with GF120918 in wild mice. Most notably, GF120918 provided tissue-specific effects in mdr1a/1b knockout mice with enhanced (p < 0.05) drug accumulation in the brain ( approximately 21-fold) and heart (3.3-fold). Our results suggest mdr1a/1b-independant mechanisms may also contribute to nelfinavir tissue distribution in mice. | lld:pubmed |
| pubmed-article:15858856 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15858856 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15858856 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15858856 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15858856 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:15858856 | pubmed:issn | 0022-3549 | lld:pubmed |
| pubmed-article:15858856 | pubmed:author | pubmed-author:KellyEdward... | lld:pubmed |
| pubmed-article:15858856 | pubmed:author | pubmed-author:HoRodney J... | lld:pubmed |
| pubmed-article:15858856 | pubmed:author | pubmed-author:SalamaNoha... | lld:pubmed |
| pubmed-article:15858856 | pubmed:author | pubmed-author:BuiTotT | lld:pubmed |
| pubmed-article:15858856 | pubmed:copyrightInfo | (c) 2005 Wiley-Liss, Inc. | lld:pubmed |
| pubmed-article:15858856 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15858856 | pubmed:volume | 94 | lld:pubmed |
| pubmed-article:15858856 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15858856 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15858856 | pubmed:pagination | 1216-25 | lld:pubmed |
| pubmed-article:15858856 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:meshHeading | pubmed-meshheading:15858856... | lld:pubmed |
| pubmed-article:15858856 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15858856 | pubmed:articleTitle | The impact of pharmacologic and genetic knockout of P-glycoprotein on nelfinavir levels in the brain and other tissues in mice. | lld:pubmed |
| pubmed-article:15858856 | pubmed:affiliation | Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA. | lld:pubmed |
| pubmed-article:15858856 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15858856 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15858856 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:15858856 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15858856 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15858856 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15858856 | lld:pubmed |
