Rectal controlled-release morphine: plasma levels of morphine and its metabolites following the rectal administration of MST Continus 100 mg.

Abstract

Eight patients undergoing major maxillary surgery were given sustained-release morphine (100 mg MST Continus) rectally, immediately after induction of general anaesthesia. Blood samples for assay were taken just prior to morphine administration, together with a further 11 samples over the following 24 h. Assay of the plasma for morphine, morphine-3-glucuronide and morphine-6-glucuronide was carried out using a validated high-performance liquid chromatography technique. Morphine Tmax ranged from 3 h to 12 h (median 6 h), Cmax 8.0-40.0 ng/ml and AUC0-24 90.1-429.7 ng/h/ml in subjects offering blood samples over the 24-h period. Likewise, morphine-3-glucuronide Tmax ranged from 3 h to 24 h (median 9 h), Cmax 153-370 ng/ml and AUC0-24 2776-4390 ng/h/ml. Morphine-6-glucuronide Tmax ranged from 8 h to 12 h (median 10 h), Cmax 24-59 ng/ml and AUC0-24 137-803 ng/h/ml. Morphine and morphine metabolite AUC0-24 ratios were calculated, but they did not correlate with analgesic needs. The AUC0-24 ratios were similar to those following 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 suitable for acute pain, because analgesic requirements change much more rapidly than in the chronic pain situation where individual patient titration can take place.