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Oxycodone pharmacokinetics and pharmacodynamics in the rat in the presence of the P-glycoprotein inhibitor PSC833

Authors

  • Emma Boström,

    1. Department of Biopharmaceutical Sciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Uppsala, Sweden
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  • Ulrika S.H. Simonsson,

    1. Department of Biopharmaceutical Sciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Uppsala, Sweden
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  • Margareta Hammarlund-Udenaes

    Corresponding author
    1. Department of Biopharmaceutical Sciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Uppsala, Sweden
    • Department of Biopharmaceutical Sciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Uppsala, Sweden. Telephone: +46-(0) 18 471 4300; Fax: +46-(0) 18 471 4003
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Abstract

The objective of this study was to investigate the in vivo influence of the P-glycoprotein (P-gp) inhibitor PSC833 on the plasma pharmacokinetics, total brain concentrations and tail-flick latency of oxycodone in rats. Eight rats each received an infusion of PSC833 or vehicle without PSC833. One hour later, all animals received 0.3 mg/kg oxycodone as a 1-h infusion. Plasma samples were taken, and tail-flick latency was monitored during the infusion and for 2 h thereafter. The brains were collected at the end of the experiment. There were no differences between the two groups in area under the plasma oxycodone concentration-time curve from time zero to infinity, or oxycodone plasma clearance, volume of distribution at steady-state, or half-life. There were no differences in average total brain oxycodone concentrations at 180 min, nor were there any differences in average tail-flick latency for the PSC833 and control groups. In conclusion, coadministration of PSC833 did not alter the plasma pharmacokinetics, brain concentrations, or associated tail-flick latency of oxycodone, indicating that oxycodone is not a P-gp substrate in the rat. This has important clinical implications, as it indicates that oxycodone, unlike some other opioids, will not interact at the blood–brain barrier (BBB) with concomitantly administered P-gp substrates. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1060–1066, 2005

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