{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:38:55Z","timestamp":1790185135374,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The purpose of this study was to determine the pharmacokinetics of [14C]diclofenac, [14C]salicylate and [3H]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. 99mTc-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s\u22121) and fractions of solute unbound in the perfusate were in the order: diclofenac &amp;gt;salicylate &amp;gt;clonidine &amp;gt;sucrose (from 41.8 to 0.10 mL s\u22121). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.<\/jats:p>","DOI":"10.1211\/0022357021778619","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T20:14:04Z","timestamp":1034367244000},"page":"373-382","source":"Crossref","is-referenced-by-count":6,"title":["Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model"],"prefix":"10.1093","volume":"54","author":[{"given":"K A","family":"Foster","sequence":"first","affiliation":[{"name":"Therapeutics Research Unit, Department of Medicine, University of Queensland, Princess Alexandra Hospital , Ipswich Road, Woolloongabba, Queensland 4102,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Weiss","sequence":"additional","affiliation":[{"name":"Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University , Halle-Wittenberg 06112,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M S","family":"Roberts","sequence":"additional","affiliation":[{"name":"Therapeutics Research Unit, Department of Medicine, University of Queensland, Princess Alexandra Hospital , Ipswich Road, Woolloongabba, Queensland 4102,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,3,1]]},"reference":[{"key":"2024103109383985200_cit1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1152\/jappl.1967.22.5.1033","article-title":"An isolated, perfused rat brain preparation, its spontaneous and stimulated activity","volume":"22","author":"Andjus","year":"1967","journal-title":"J. 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