RECTAL CONTROLLED-RELEASE MORPHINE - PLASMA-LEVELS OF MORPHINE AND ITS METABOLITES FOLLOWING THE RECTAL ADMINISTRATION OF MST CONTINUS 100 MG

Eight patients undergoing major maxillary surgery were given sustained -release morphine (100 mg MST Continus) rectally, immediately after in duction of general anaesthesia. Blood samples for assay were taken jus t prior to morphine administration, together with a further II samples over the following 24 h. Assay of the plasma for morphine, morphine-3 -glucuronide and morphine-6-glucuronide was carried out using a valida ted high-performance liquid chromatography technique,Morphine T-max ra nged from 3 h to 12 h (median 6 h), C-max 8.0-40.0 ng/ml and AUC(0-24) 90.1-429.7 ng/h/ml in subjects offering blood samples over the 24-h p eriod. Likewise, morphine-3-glucuronide T-max ranged from 3 h to 24 h (median 9 h), C-max 153-370 ng/ml and AUC(0-24) 2776-4390 ng/h/ml. Mor phine-6-glucuronide T-max ranged from 8 h to 12 h (median 10 h), C-max 24-59 ng/ml and AUC(0-24) 137-803 ng/h/ml. Morphine and morphine meta bolite AUC(0-24) ratios were calculated, but they did not correlate wi th analgesic needs. The AUC(0-24) ratios were similar to those followi ng oral and rectal dosing in other studies involving cancer patients. The wide variation of individual morphine and metabolite plasma levels , and their AUC ratios indicates considerable interpatient variability in the absorption and metabolism of rectal sustained-release morphine , This large interpatient variation may indicate that it is not suitab le for acute pain, because analgesic requirements change much more rap idly than in the chronic pain situation where individual patient titra tion can take place.