Active Uptake of Oxycodone at Both the Blood-Cerebrospinal Fluid Barrier and The Blood-Brain Barrier without Sex Differences: A Rat Microdialysis Study

Oxycodone is actively transported across the blood-brain barrier via a proton-coupled organic cation antiporter system, but the extent of this active uptake at the blood-cerebrospinal fluid barrier (BCSFB), and whether it differs by sex, was not well understood. This study used intracerebral microdialysis in male and female Sprague-Dawley rats receiving intravenous oxycodone to compare drug transport across the blood-brain barrier and BCSFB, with pharmacokinetic analysis performed using Phoenix WinNonlin. Active uptake was confirmed at both barriers, though transport was significantly lower at the BCSFB than the blood-brain barrier, with no significant sex differences observed in either brain delivery or systemic pharmacokinetics. The findings suggest cerebrospinal fluid may serve as an acceptable, if somewhat conservative, surrogate for brain interstitial fluid when studying oxycodone and other actively transported drugs.