title: Systematic review of factors affecting the ratios of morphine and its major metabolites.
abstract: In a systematic review of 57 studies with information on 1232 patients we examined the effect of age, renal impairment, route of administration, and method of analysis on the ratios of morphine-3-glucuronide:morphine (M3G:M) and morphine-6-glucuronide:morphine (M6G:M) and the relative concentrations of M3G and M6G. Across all studies the range of the ratios of metabolites to morphine was wide (0.001-504 for M3G:M, and 0-97 for M6G:M). Neonates produced morphine glucuronides at a lower rate than older children or adults. Metabolite ratios were higher in renal impairment. Routes of administration which avoided first pass metabolism (intravenous, transdermal, rectal, intramuscular, epidural and intrathecal) resulted in lower metabolite production than oral, buccal or sublingual. Metabolite production was similar for single and multiple dosing. There was no evidence of differences between methods of assay. There was a high correlation between the two glucuronide metabolites in spite of the different situations studied, supporting a single glucuronidating enzyme. Morphine was present in CSF at a fourfold higher concentration than the glucuronide metabolites.
authors.affiliation: Departamento de Farmacologia, Instituto de Neurociencias, Universidad Miguel Hernández, Campus de San Juan, 03080 Alicante, Spain Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospital, The Churchill, Headington, Oxford OX3 7LJ, UK.
authors.forename: Clara C
authors.initials: CC
authors.lastname: Faura
authors.forename: Sally L
authors.initials: SL
authors.lastname: Collins
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Moore
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McQuay
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006801:Humans; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000378:metabolism*; D009020:Morphine / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009022:Morphine Derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide