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• W2082959774 endingPage "1631" @default.
• W2082959774 startingPage "1624" @default.
• W2082959774 abstract "The blood-brain barrier (BBB) transport of oxycodone was studied in rats. Microdialysis probes were inserted into the striatum and vena jugularis. Ten animals were given a bolus dose followed by a 120-min constant rate infusion to study the steady-state concepts of oxycodone BBB equilibration. Another 10 animals were given a 60-min constant rate infusion to study the rate of equilibration across the BBB. Oxycodone-D3 was used as a calibrator for the microdialysis experiments. The samples were analyzed with a liquid chromatography-tandem mass spectrometry method and a population pharmacokinetic model was used to simultaneously fit all the data using NONMEM. A two-compartment model which allowed for a delay between the venous and arterial compartments best described the pharmacokinetics for oxycodone in blood and plasma, whereas a one-compartment model was sufficient to describe the pharmacokinetics in the brain. The BBB transport of oxycodone was parameterized as CL(in) and K(p,uu). CL(in) describes the clearance of oxycodone across the BBB into the brain, whereas K(p,uu) describes the extent of drug equilibration across the BBB. CL(in) across the BBB was estimated to 1910 microl/min x g brain. K(p,uu) was estimated to 3.0, meaning that the unbound concentration of oxycodone in brain was 3 times higher than in blood, which is an indication of active influx of oxycodone at the BBB. This is the first evidence of an opioid having an unbound steady-state concentration in brain that is higher than unity, which can explain potency discrepancies between oxycodone and other opioids." @default.
• W2082959774 created "2016-06-24" @default.
• W2082959774 creator A5013955124 @default.
• W2082959774 creator A5073688072 @default.
• W2082959774 creator A5091428143 @default.
• W2082959774 date "2006-06-08" @default.
• W2082959774 modified "2023-10-06" @default.
• W2082959774 title "In Vivo Blood-Brain Barrier Transport of Oxycodone in the Rat: Indications for Active Influx and Implications for Pharmacokinetics/Pharmacodynamics" @default.
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• W2082959774 doi "https://doi.org/10.1124/dmd.106.009746" @default.
• W2082959774 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16763013" @default.
• W2082959774 hasPublicationYear "2006" @default.
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