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dc.contributor.authorVillesen, H.en
dc.contributor.authorFoster, D.en
dc.contributor.authorUpton, R.en
dc.contributor.authorSomogyi, A.en
dc.contributor.authorMartinez, A.en
dc.contributor.authorGrant, C.en
dc.identifier.citationJournal of Pharmaceutical Sciences, 2006; 95(8):1666-1676en
dc.descriptionPublished in Journal of Pharmaceutical Sciences, 2006; 95 (8):1666-1676 at www.interscience.wiley.comen
dc.description.abstractOxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebral kinetics of oxycodone was quantified using a conscious chronically instrumented sheep preparation. Five sheep were administered oxycodone as intravenous infusions (30 mg over 4 min). Using hybrid physiologically based kinetic models, cerebral kinetics was estimated from arterio-sagittal sinus concentration gradients and cerebral blood flow (CBF). A two-compartment membrane-limited model best described the data. The volume of the first brain compartment was 35.4 mL with a half-life of equilibrium of 0.6 min. The brain:blood equilibration of oxycodone was relatively slow (half-life of 7.2 min), with a large deep cerebral distribution volume (222.8 mL) for the second compartment and a moderate membrane permeability of 54.8 mL/min, which exceeded the nominal CBF (40 mL/min). Drug retention in the brain was 1.3% after 45 min. In conclusion, pharmacokinetic modelling of oxycodone showed a delayed equilibration between brain and blood of a nature that would be affected by changes in both CBF and blood brain barrier permeability.en
dc.description.statementofresponsibilityHanne H. Villesen, David J.R. Foster, Richard N. Upton, Andrew A. Somogyi, Allison Martinez, Cliff Granten
dc.publisherJohn Wiley & Sons Incen
dc.subjectOxycodone; pharmacokinetics; distribution; blood brain barrier; blood flow; physiological model; sheepen
dc.titleCerebral kinetics of oxycodone in conscious sheepen
dc.typeJournal articleen
pubs.library.collectionAnaesthesia and Intensive Care publicationsen
dc.identifier.orcidSomogyi, A. [0000-0003-4779-0380]en
Appears in Collections:Anaesthesia and Intensive Care publications

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