{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:31:57Z","timestamp":1791192717144,"version":"4.1.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0118638","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T18:01:21Z","timestamp":1430503281000},"page":"e0118638","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Validation of a P-Glycoprotein (P-gp) Humanized Mouse Model by Integrating Selective Absolute Quantification of Human MDR1, Mouse Mdr1a and Mdr1b Protein Expressions with In Vivo Functional Analysis for Blood-Brain Barrier Transport"],"prefix":"10.1371","volume":"10","author":[{"given":"Muhammad Waqas","family":"Sadiq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Hoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Tachikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Terasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Hammarlund-Udenaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,5,1]]},"reference":[{"issue":"2","key":"ref1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1471-4159.2011.07208.x","article-title":"Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors","volume":"117","author":"Y Uchida","year":"2011","journal-title":"Journal of neurochemistry"},{"issue":"18","key":"ref2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/0024-3205(92)90537-Y","article-title":"P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells","volume":"51","author":"A Tsuji","year":"1992","journal-title":"Life sciences"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0005-2736(76)90160-7","article-title":"A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants","volume":"455","author":"RL Juliano","year":"1976","journal-title":"Biochimica et biophysica acta"},{"issue":"2\u20133","key":"ref4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0169-409X(98)00085-4","article-title":"P-Glycoprotein, a gatekeeper in the blood-brain barrier","volume":"36","author":"AH Schinkel","year":"1999","journal-title":"Advanced drug delivery reviews"},{"issue":"12","key":"ref5","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1002\/jps.20686","article-title":"Kinetic analyses for species differences in P-glycoprotein-mediated drug transport","volume":"95","author":"M Katoh","year":"2006","journal-title":"Journal of pharmaceutical sciences"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1124\/dmd.108.024745","article-title":"Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport","volume":"37","author":"S Syvanen","year":"2009","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev.bi.62.070193.002125","article-title":"Biochemistry of multidrug resistance mediated by the multidrug transporter","volume":"62","author":"MM Gottesman","year":"1993","journal-title":"Annual review of biochemistry"},{"issue":"20","key":"ref8","doi-asserted-by":"crossref","first-page":"12053","DOI":"10.1016\/S0021-9258(18)80173-9","article-title":"Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes","volume":"264","author":"SI Hsu","year":"1989","journal-title":"The Journal of biological chemistry"},{"issue":"4","key":"ref9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0092-8674(94)90212-7","article-title":"Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs","volume":"77","author":"AH Schinkel","year":"1994","journal-title":"Cell"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.clpt.2005.01.022","article-title":"Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography","volume":"77","author":"L Sasongko","year":"2005","journal-title":"Clinical pharmacology and therapeutics"},{"issue":"9","key":"ref11","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1002\/jps.20658","article-title":"Development of a P-glycoprotein knockout model in rodents to define species differences in its functional effect at the blood-brain barrier","volume":"95","author":"L Cutler","year":"2006","journal-title":"Journal of pharmaceutical sciences"},{"key":"ref12","first-page":"253","article-title":"Manipulating the Mouse Embryo: A Laboratory Manual","author":"BLM Hogan","year":"1994"},{"issue":"9","key":"ref13","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1172\/JCI35483","article-title":"A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response","volume":"118","author":"N Scheer","year":"2008","journal-title":"J Clin Invest"},{"issue":"9","key":"ref14","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1124\/dmd.107.015222","article-title":"In vitro methods for estimating unbound drug concentrations in the brain interstitial and intracellular fluids","volume":"35","author":"M Friden","year":"2007","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/jps.10332","article-title":"Development and validation of a 96-well equilibrium dialysis apparatus for measuring plasma protein binding","volume":"92","author":"MJ Banker","year":"2003","journal-title":"Journal of pharmaceutical sciences"},{"issue":"6","key":"ref16","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1124\/dmd.108.026377","article-title":"Development of a high-throughput brain slice method for studying drug distribution in the central nervous system","volume":"37","author":"M Friden","year":"2009","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2045-8118-10-6","article-title":"The brain slice method for studying drug distribution in the CNS","volume":"10","author":"I Loryan","year":"2013","journal-title":"Fluids and barriers of the CNS"},{"issue":"2","key":"ref18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/00001756-199311180-00008","article-title":"Comparison of double fluorescence staining and LDH-test for monitoring cell viability in vitro","volume":"5","author":"G Keilhoff","year":"1993","journal-title":"NeuroReport"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0168-3659(95)00007-U","article-title":"In vitro cytotoxicity of macromolecules in different cell culture systems","volume":"34","author":"S Choksakulnimitr","year":"1995","journal-title":"Journal of Controlled Release"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/jcbfm.2009.200","article-title":"Improved measurement of drug exposure in the brain using drug-specific correction for residual blood","volume":"30","author":"M Friden","year":"2010","journal-title":"Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1124\/dmd.110.035998","article-title":"Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods","volume":"39","author":"M Friden","year":"2011","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1007\/s11095-008-9532-4","article-title":"Quantitative atlas of membrane transporter proteins: development and application of a highly sensitive simultaneous LC\/MS\/MS method combined with novel in-silico peptide selection criteria","volume":"25","author":"J Kamiie","year":"2008","journal-title":"Pharmaceutical research"},{"issue":"6","key":"ref23","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1124\/dmd.112.044719","article-title":"Quantitative proteomics of transporter expression in brain capillary endothelial cells isolated from P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and P-gp\/Bcrp knockout mice","volume":"40","author":"S Agarwal","year":"2012","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"issue":"1","key":"ref24","first-page":"9","article-title":"Pharmacological insights from P-glycoprotein knockout mice","volume":"36","author":"AH Schinkel","year":"1998","journal-title":"International journal of clinical pharmacology and therapeutics"},{"issue":"4","key":"ref25","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2174\/1389200033489415","article-title":"Utility of Mdr1-gene deficient mice in assessing the impact of P-glycoprotein on pharmacokinetics and pharmacodynamics in drug discovery and development","volume":"4","author":"C Chen","year":"2003","journal-title":"Current drug metabolism"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1124\/mi.9.3.7","article-title":"Pharmacokinetic assessment of multiple ATP-binding cassette transporters: the power of combination knockout mice","volume":"9","author":"JS Lagas","year":"2009","journal-title":"Molecular interventions"},{"issue":"4","key":"ref27","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1172\/JCI118214","article-title":"Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A","volume":"96","author":"AH Schinkel","year":"1995","journal-title":"J Clin Invest"},{"issue":"7","key":"ref28","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/sj.bjp.0701979","article-title":"Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography","volume":"124","author":"NH Hendrikse","year":"1998","journal-title":"British journal of pharmacology"},{"issue":"8","key":"ref29","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.ejca.2004.01.024","article-title":"Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoprotein","volume":"40","author":"EM Kemper","year":"2004","journal-title":"European journal of cancer (Oxford, England: 1990)"},{"issue":"8","key":"ref30","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s11095-007-9502-2","article-title":"On the rate and extent of drug delivery to the brain","volume":"25","author":"M Hammarlund-Udenaes","year":"2008","journal-title":"Pharmaceutical research"},{"issue":"9","key":"ref31","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1124\/dmd.106.009746","article-title":"In vivo blood-brain barrier transport of oxycodone in the rat: indications for active influx and implications for pharmacokinetics\/pharmacodynamics","volume":"34","author":"E Bostrom","year":"2006","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"issue":"9","key":"ref32","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1002\/jps.22567","article-title":"Diphenhydramine active uptake at the blood-brain barrier and its interaction with oxycodone in vitro and in vivo","volume":"100","author":"MW Sadiq","year":"2011","journal-title":"Journal of pharmaceutical sciences"},{"issue":"9","key":"ref33","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1002\/jps.23492","article-title":"Oxymorphone active uptake at the blood-brain barrier and population modeling of its pharmacokinetic-pharmacodynamic relationship","volume":"102","author":"MW Sadiq","year":"2013","journal-title":"Journal of pharmaceutical sciences"},{"issue":"5","key":"ref34","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/jps.20327","article-title":"Oxycodone pharmacokinetics and pharmacodynamics in the rat in the presence of the P-glycoprotein inhibitor PSC833","volume":"94","author":"E Bostrom","year":"2005","journal-title":"Journal of pharmaceutical sciences"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0118638","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T23:39:04Z","timestamp":1651880344000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0118638"}},"subtitle":[],"editor":[{"given":"M\u00e1ria A.","family":"Deli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,5,1]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,5,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0118638","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,1]]}}}