MORPHINE, MORPHINE-6-GLUCURONIDE, AND MORPHINE-3-GLUCURONIDE IN CEREBROSPINAL-FLUID AND PLASMA AFTER EPIDURAL ADMINISTRATION OF MORPHINE

Background and Objectives. It has been suggested that the potency of e pidural morphine might be explained by spinal metabolism to the active and potent metabolite morphine-6-glucuronide (M6G). The main objectiv e of this study was to describe the early pharmacokinetics of epidural ly administered, morphine with special attention to the appearance of the glucuronated metabolites in cerebrospinal fluid (CSP). Methods. Mo rphine was administered epidurally to eight patients scheduled for maj or abdominal surgery. The concentrations of morphine and its 6-glucuro nide and 3-glucuronide metabolites were monitored in blood and CSF at 10, 30, 60, and 120 minutes and 10 and 24 hours. Postoperative pain wa s estimated on a visual analog scale, and analgesia requirements (admi nistered by a patient-controlled techique) were recorded. Results. Onl y traces of the metabolites were found in CSF and in only two patients throughout the 24 hours. Both metabolites appeared rapidly (within 30 minutes) in plasma in all patients and were found in plasma throughou t the study period. Morphine concentration peaked in CSF within 30 min utes at a very high level; in plasma, it peaked at 10 minutes. No corr elation was seen between initial or later concentrations of morphine i n CSF and postoperative pain or morphine requirements. Conclusions. No evidence of spinal metabolism of morphine could be found. Rapid distr ibution of morphine to CSP and plasma occurred after epidural administ ration. No value of initial CSF morphine concentrations for prediction of analgesic requirements could be demonstrated.