Oxycodone Pharmacokinetics and Pharmacodynamics in the Rat in the Presence of the P-Glycoprotein Inhibitor PSC833
2005 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 94, no 5, 1060-1066 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 94, no 5, 1060-1066 p.
P-glycoprotein, pharmacokineties/pharmacodynamics, blood-brain barrier, efflux pumps, active transports, transporters, CNS, clearance
IdentifiersURN: urn:nbn:se:uu:diva-95635DOI: 10.1002/jps.20327ISI: 000228792200014PubMedID: 15799017OAI: oai:DiVA.org:uu-95635DiVA: diva2:169932