{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:22:45Z","timestamp":1791030165510,"version":"4.1.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2007,9]]},"DOI":"10.1124\/dmd.107.015222","type":"journal-article","created":{"date-parts":[[2007,6,26]],"date-time":"2007-06-26T00:40:01Z","timestamp":1182818401000},"page":"1711-1719","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":185,"title":["In Vitro Methods for Estimating Unbound Drug Concentrations in the Brain Interstitial and Intracellular Fluids"],"prefix":"10.1016","volume":"35","author":[{"given":"Markus","family":"Frid\u00e9n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anubha","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Antonsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Bredberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Hammarlund-Udenaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/dmd.107.015222_bib1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.neuint.2003.11.006","article-title":"Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology","volume":"45","author":"Abbott","year":"2004","journal-title":"Neurochem Int"},{"key":"10.1124\/dmd.107.015222_bib2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2307\/2987937","article-title":"Measurement in medicine: the analysis of method comparison studies","volume":"32","author":"Altman","year":"1983","journal-title":"The Statistician"},{"key":"10.1124\/dmd.107.015222_bib3","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1021\/jm960073m","article-title":"Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates","volume":"39","author":"Avdeef","year":"1996","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.107.015222_bib4","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1124\/dmd.105.007914","article-title":"Evaluation of the utility of brain slice methods to study brain penetration","volume":"34","author":"Becker","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.107.015222_bib5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/096228029900800204","article-title":"Measuring agreement in method comparison studies [see comment]","volume":"8","author":"Bland","year":"1999","journal-title":"Stat Methods Med Res"},{"key":"10.1124\/dmd.107.015222_bib6","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":"Bostrom","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.107.015222_bib7","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1038\/sj.bjp.0704406","article-title":"Blood-brain barrier transport and brain distribution of morphine-6-glucuronide in relation to the antinociceptive effect in rats\u2014pharmacokinetic\/pharmacodynamic modelling","volume":"134","author":"Bouw","year":"2001","journal-title":"Br J Pharmacol"},{"key":"10.1124\/dmd.107.015222_bib8","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/00004647-200002000-00020","article-title":"Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice","volume":"20","author":"Dagenais","year":"2000","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.1124\/dmd.107.015222_bib9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1124\/pr.58.2.3","article-title":"Multidrug resistance-associated proteins: expression and function in the central nervous system","volume":"58","author":"Dallas","year":"2006","journal-title":"Pharmacol Rev"},{"key":"10.1124\/dmd.107.015222_bib10","series-title":"Physiology of the CSF and Blood-Brain Barriers","first-page":"459","article-title":"Acid-base relations in the central nervous system","author":"Davson","year":"1996"},{"key":"10.1124\/dmd.107.015222_bib11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.2165\/00003088-200241100-00001","article-title":"Considerations in the use of cerebrospinal fluid pharmacokinetics to predict brain target concentrations in the clinical setting: implications of the barriers between blood and brain","volume":"41","author":"de Lange","year":"2002","journal-title":"Clin Pharmacokinet"},{"key":"10.1124\/dmd.107.015222_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0006-8993(94)90276-3","article-title":"Critical factors of intracerebral microdialysis as a technique to determine the pharmacokinetics of drugs in rat brain","volume":"666","author":"de Lange","year":"1994","journal-title":"Brain Res"},{"key":"10.1124\/dmd.107.015222_bib13","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1172\/JCI114279","article-title":"Plasma binding and transport of diazepam across the blood-brain barrier. No evidence for in vivo enhanced dissociation","volume":"84","author":"Dubey","year":"1989","journal-title":"J Clin Invest"},{"key":"10.1124\/dmd.107.015222_bib14","series-title":"Nanomedicine, vol I: Basic Capabilities","author":"Freitas","year":"1999"},{"key":"10.1124\/dmd.107.015222_bib15","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1124\/dmd.105.007211","article-title":"Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu)","volume":"34","author":"Gupta","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.107.015222_bib16","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1002\/rcm.1983","article-title":"Quantitative determination of cetirizine enantiomers in guinea pig plasma, brain tissue and microdialysis samples using liquid chromatography\/tandem mass spectrometry","volume":"19","author":"Gupta","year":"2005","journal-title":"Rapid Commun Mass Spectrom"},{"key":"10.1124\/dmd.107.015222_bib17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1023\/A:1012080106490","article-title":"Drug equilibration across the blood-brain barrier\u2014pharmacokinetic considerations based on the microdialysis method","volume":"14","author":"Hammarlund-Udenaes","year":"1997","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.107.015222_bib18","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/S0022-3565(25)13107-8","article-title":"Brain efflux index as a novel method of analyzing efflux transport at the blood-brain barrier","volume":"277","author":"Kakee","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.107.015222_bib19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/bdd.325","article-title":"Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discovery","volume":"23","author":"Kalvass","year":"2002","journal-title":"Biopharm Drug Dispos"},{"key":"10.1124\/dmd.107.015222_bib20","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1023\/A:1015040217741","article-title":"Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs","volume":"16","author":"Kelder","year":"1999","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.107.015222_bib21","series-title":"Principles and Practice of Positron Emission Tomography","first-page":"65","article-title":"Data analysis and image processing","author":"Koeppe","year":"2002"},{"key":"10.1124\/dmd.107.015222_bib22","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1046\/j.1600-0773.2003.pto930505.x","article-title":"Effect of probenecid and quinidine on the transport of alovudine (3\u2032-fluorothymidine) to the rat brain studied by microdialysis","volume":"93","author":"Linden","year":"2003","journal-title":"Pharmacol Toxicol"},{"key":"10.1124\/dmd.107.015222_bib23","series-title":"Brain Slices","first-page":"113","article-title":"Energy metabolism and brain slice function","author":"Lipton","year":"1984"},{"key":"10.1124\/dmd.107.015222_bib24","first-page":"505","article-title":"Strategies to optimize brain penetration in drug discovery","volume":"8","author":"Liu","year":"2005","journal-title":"Curr Opin Drug Discov Devel"},{"key":"10.1124\/dmd.107.015222_bib25","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1124\/dmd.105.008201","article-title":"Evaluation of cerebrospinal fluid concentration and plasma free concentration as a surrogate measurement for brain free concentration","volume":"34","author":"Liu","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.107.015222_bib26","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/bdd.328","article-title":"Investigation of the high partition of YM992, a novel antidepressant, in rat brain\u2014in vitro and in vivo evidence for the high binding in brain and the high permeability at the BBB","volume":"23","author":"Mano","year":"2002","journal-title":"Biopharm Drug Dispos"},{"key":"10.1124\/dmd.107.015222_bib27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/oxfordjournals.bja.a013385","article-title":"Microdialysis study of the bloodbrain equilibration of thiopental enantiomers","volume":"84","author":"Mather","year":"2000","journal-title":"Br J Anaesth"},{"key":"10.1124\/dmd.107.015222_bib28","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1111\/j.1471-4159.1992.tb10053.x","article-title":"Simultaneous measurement of extracellular morphine and serotonin in brain tissue and CSF by microdialysis in awake rats","volume":"58","author":"Matos","year":"1992","journal-title":"J Neurochem"},{"key":"10.1124\/dmd.107.015222_bib29","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-2236(98)01261-2","article-title":"Extracellular space structure revealed by diffusion analysis [see comment]","volume":"21","author":"Nicholson","year":"1998","journal-title":"Trends Neurosci"},{"key":"10.1124\/dmd.107.015222_bib30","first-page":"784","article-title":"Quantitative brain microdialysis study on the mechanism of quinolones distribution in the central nervous system","volume":"25","author":"Ooie","year":"1997","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.107.015222_bib31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/jcbfm.1983.1","article-title":"Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data","volume":"3","author":"Patlak","year":"1983","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.1124\/dmd.107.015222_bib32","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1023\/A:1011049830615","article-title":"Lipophilicity behaviour of the Zwitterionic antihistamine cetirizine in phosphatidylcholine liposomes\/water systems","volume":"18","author":"Plember van Balen","year":"2001","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.107.015222_bib33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S1056-8719(97)00053-1","article-title":"Tissue water content in rats measured by desiccation","volume":"38","author":"Reinoso","year":"1997","journal-title":"J Pharmacol Toxicol Methods"},{"key":"10.1124\/dmd.107.015222_bib34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0014-2999(97)10082-6","article-title":"Distribution of apomorphine enantiomers in plasma, brain tissue and striatal extracellular fluid","volume":"329","author":"Sam","year":"1997","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/dmd.107.015222_bib35","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.addr.2004.07.011","article-title":"Principles and applicability of CSF sampling for the assessment of CNS drug delivery and pharmacodynamics","volume":"56","author":"Shen","year":"2004","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1124\/dmd.107.015222_bib36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/0006-8993(88)90816-5","article-title":"Determination of rat cerebral cortical blood volume changes by capillary mean transit time analysis during hypoxia, hypercapnia and hyperventilation","volume":"454","author":"Shockley","year":"1988","journal-title":"Brain Res"},{"key":"10.1124\/dmd.107.015222_bib37","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1046\/j.1471-4159.1995.64052125.x","article-title":"Transport of gabapentin, a gamma-amino acid drug, by system l alpha-amino acid transporters: a comparative study in astrocytes, synaptosomes, and CHO cells","volume":"64","author":"Su","year":"1995","journal-title":"J Neurochem"},{"key":"10.1124\/dmd.107.015222_bib38","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s11095-006-9780-0","article-title":"Pharmacokinetic consequences of active drug efflux at the blood-brain barrier","volume":"23","author":"Syvanen","year":"2006","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.107.015222_bib39","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.0001-5172.2003.0311.x","article-title":"Altered brain exposure of morphine in experimental meningitis studied with microdialysis","volume":"48","author":"Tunblad","year":"2004","journal-title":"Acta Anaesthesiol Scand"},{"key":"10.1124\/dmd.107.015222_bib40","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1023\/A:1023250900462","article-title":"Morphine blood-brain barrier transport is influenced by probenecid co-administration","volume":"20","author":"Tunblad","year":"2003","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.107.015222_bib41","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/S0022-3565(25)24549-9","article-title":"Brain, liver and blood distribution kinetics of carbamazepine and its metabolic interaction with clomipramine in rats: a quantitative microdialysis study","volume":"272","author":"Van Belle","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.107.015222_bib42","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1023\/A:1016092525901","article-title":"The simultaneous estimation of the influx and efflux blood-brain barrier permeabilities of gabapentin using a microdialysis-pharmacokinetic approach","volume":"13","author":"Wang","year":"1996","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.107.015222_bib43","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/sj.bjp.0703759","article-title":"Modelling of the blood-brain barrier transport of morphine-3-glucuronide studied using microdialysis in the rat: involvement of probenecid-sensitive transport","volume":"131","author":"Xie","year":"2000","journal-title":"Br J Pharmacol"},{"key":"10.1124\/dmd.107.015222_bib44","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1023\/A:1011929910782","article-title":"Blood-brain barrier equilibration of codeine in rats studied with microdialysis","volume":"15","author":"Xie","year":"1998","journal-title":"Pharm Res"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624014338?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624014338?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/dmd.107.015222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T16:15:39Z","timestamp":1739895339000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624014338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2007,9]]}},"alternative-id":["S0090955624014338"],"URL":"https:\/\/doi.org\/10.1124\/dmd.107.015222","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2007,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"In Vitro Methods for Estimating Unbound Drug Concentrations in the Brain Interstitial and Intracellular Fluids","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/dmd.107.015222","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2007 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}