Spinal Cord and Central Nervous System Distribution of Epidural Oxycodone-Experimental Pregnant Sheep Model

Epidural oxycodone is a highly effective analgesic. However, oxycodone's distribution in the spinal cord after epidural injection is not known. In this experimental study, we evaluated the segmental spinal cord, brain, cerebrospinal fluid and plasma distribution and foetal exposure of epidurally administered oxycodone in a pregnant sheep model.

Twenty-eight pregnant ewes were given a single 0.1 mg/kg (n = 23) or 0.2 mg/kg (n = 5) epidural oxycodone bolus through a lumbar catheter. Tissue samples were collected from the spinal cord at the epidural catheter tip area, 10 cm caudal and 10, 20 and 30 cm cranial to that, brain tissue, cerebrospinal fluid and plasma after euthanasia from ewes and foetuses. The concentrations of oxycodone and its metabolites oxymorphone and noroxycodone were analysed with ultra-performance liquid chromatography mass spectrometry.

During autopsy, 23 ewes had catheters in the epidural space. The median oxycodone concentrations in the ewes' spinal cord were 9820 (IQR: 1001, 11,600) ng/g at the epidural catheter tip area, and similar at 10 cm caudal and at 10 and 20 cm cranial to that. At 30 cm cranial to the tip site, the concentration was significantly lower, 2910 (600, 8895) ng/g. Oxycodone concentrations in the ewes' brain tissues were substantially lower, IQR 53-155 ng/g, as were the plasma concentrations (IQR: 8.4-16 ng/mL) and CSF concentrations (IQR 6.1-34 ng/mL). Foetal exposure to oxycodone was negligible.

This experimental study suggests that after epidural administration, oxycodone distributes into the spinal cord in high concentrations over a relatively long area.

In this large animal experimental model involving pregnant ewes, oxycodone kinetics after epidural injection were examined for different doses. Concentrations of the test drug were measured in tissues at different times throughout the central nervous systems, after ending the experiment.