Table 1. Morphine and Morphine Metabolite Concentrations in Cisternal CSF of Sheep Chronically Infused with Lumbar Intrathecal Morphine

* All infusates were administered at a constant rate of 80 μl/day (1.92 ml/day) and prepared from Infumorph® 500 diluted with 0.9% saline (U.S. Pharmacopoeia) to give the appropriate concentration as indicated in column 3.

† All samples were collected at the end of the 28- to 30-day infusion period via  percutaneous puncture of the atlantooccipital interspace.

‡ The amount of morphine-6-glucuronide present in all samples analyzed was below the limit of quantification.

§ The presence of “granuloma” was assessed by gross and microscopic postmortem examination after approximately 28 days of morphine administration.

∥ The limit of quantification for the analytical method was 2.50 ng/ml for morphine, morphine-3-glucuronide, and morphine-6-glucuronide.

CSF = cerebrospinal fluid.