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Rectal controlled‐release morphine: plasma levels of morphine and its metabolites following the rectal administration of MST Continus 100 mg
Author(s) -
Campbell W. I.
Publication year - 1996
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.1996.tb00002.x
Subject(s) - morphine , metabolite , cmax , pharmacokinetics , analgesic , rectal administration , medicine , glucuronide , pharmacology , dosing , active metabolite , anesthesia
Summary 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 T max ranged 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 period. 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. Morphine‐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 metabolite AUC 0–24 ratios were calculated, but they did not correlate with analgesic needs. The AUC 0–24 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.