Distribution of Morphine 6-Glucuronide and Morphine Across the Blood-Brain Barrier in Awake, Freely Moving Rats

Microdialysis was used to sample morphine 6-glucuronide (M6G) and morphine in striatal extracellular fluid after systemic administration in awake, freely moving rats. Morphine or M6G (25-67 p.moVkg) was given subcutaneously, and blood and striatal dialysate were sampled repeatedly during 1 20 mm. Blood samples were obtained by indwelling catheters in the inferior vena cava. Opiates in serum or brain dialysate were analyzed with high-performance liquid chromatography. The functional intactness of the blood-brain barrier was verified by the use of sodium technetate (Na99’TcO4). The fractional pen-etration into the brain of morphine and M60 was approximately 350- and 90-fold higher than that of Na#{176}#{176}TcO4,respectively, with a relative difference in the transfer of morphine and M6G of about 4. No hydrolysis of M6G to morphine was detected