CSF and plasma pharmacokinetics of intramuscular morphine

Morphine concentrations in plasma and cerebrospinal fluid (CSF) were measured in 58 elderly patients after intramuscular administration of 10 mg morphine. The assay employed gas chromatography with electron capture detection. From 49 of the patients undergoing urological procedures plasma and lumbar CSF samples were obtained simultaneously as spinal analgesia was given, and in addition, repeated venous samples were obtained over 4 hours from 35 of the patients. A plasma-morphine concentration vs time plot was drawn from the mean values and a CSF-morphine vs time plot was calculated by pooling individual CSF concentrations and using the sliding mean technique. The individual CSF/plasma-morphine concentration ratio vs time was also plotted. In addition, 2 or 3 CSF and plasma samples were collected simultaneously from 3 patients undergoing thoracotomy. Large interindividual variation in the CSF concentration was found. The peak CSF level was reached after 3 h and, following pseudoequilibrium, CSF-morphine levels appeared only slightly lower than those found in plasma. The availability to spinal CSF amounted to no more than 0.005% of the administered dose. CSF-morphine concentrations were not related to plasma protein or albumin concentrations.