{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:28:55Z","timestamp":1791142135926,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,1,11]],"date-time":"2012-01-11T00:00:00Z","timestamp":1326240000000},"content-version":"vor","delay-in-days":2780,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Background<\/jats:italic>. In patients with pain of malignant origin morphine may be administered in high and often increasing doses during extended periods of time. In patients with chronic pain of non\u2010malignant origin morphine may be an important remedy, and in these cases the goal is to keep the morphine dose stable. The pharmacokinetic as well as the pharmacodynamic consequences of long\u2010term morphine treatment with special reference to the two most important metabolites of morphine morphine\u20106\u2010glucuronide (M\u20106\u2010G) and morphine\u20103\u2010glucuronide (M\u20103\u2010G) remain to be settled.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. Assessments for pain, sedation and other morphine induced side effects were made several times for 19 cancer patients treated with changing doses of oral sustained release (SR) morphine and twice for 17 non\u2010cancer patients treated with stable doses of SR morphine. Blood samples were obtained simultaneously and analysed for contents of morphine, M\u20103\u2010G and M\u20106\u2010G by high\u2010performance liquid chromatography (HPLC).<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. Significant correlations were found between the daily dose of SR morphine and plasma morphine (<jats:italic>r<\/jats:italic>=0.469, <jats:italic>p<\/jats:italic>&lt;0.01), plasma M\u20106\u2010G (<jats:italic>r<\/jats:italic>=0.677, <jats:italic>p<\/jats:italic>&lt;0.01) and plasma M\u20103\u2010G (<jats:italic>r<\/jats:italic>=0.827, <jats:italic>p<\/jats:italic>&lt;0.01) in the cancer patient group, but only between the daily dose of SR morphine and plasma M\u20103\u2010G (0.662, <jats:italic>p<\/jats:italic>&lt;0.01) and plasma M\u20106\u2010G (0.571, <jats:italic>p<\/jats:italic>&lt;0.01) in the non\u2010cancer patient group. Normalised M\u20103\u2010G\/M and M\u20106\u2010G\/M ratios for the cancer patient group were independent of duration of treatment and daily dose of SR morphine. Likewise in the non\u2010cancer patient group duration of treatment did not influence the metabolite ratios. Correlations between pain score and plasma morphine, M\u20106\u2010G and M\u20106\u2010G\/M were weak in the cancer patient as well as in the non\u2010cancer patient group making it impossible to draw any conclusion regarding the potential contributory analgesic effect of M\u20106\u2010G. Dryness of the mouth was the most frequent adverse effect reported in the non\u2010cancer as well as the cancer patient group. In the latter group patients complaining of dryness of the mouth had significantly higher plasma morphine and M\u20106\u2010G concentrations than patients who did not suffer from this side effect. This difference persisted (or was close to significance) when excluding patients receiving antidepressants.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>. In the cancer patient group neither dose nor treatment period seems to influence morphine glucuronidation. Likewise in the non\u2010cancer patient group receiving stable doses of morphine duration of treatment does not seem to influence morphine glucuronidation. Dryness of the mouth was positively correlated to high plasma concentrations of morphine and M\u20106\u2010G.<\/jats:p>","DOI":"10.1016\/j.ejpain.2003.09.003","type":"journal-article","created":{"date-parts":[[2003,11,15]],"date-time":"2003-11-15T12:01:05Z","timestamp":1068897665000},"page":"263-271","source":"Crossref","is-referenced-by-count":14,"title":["Pharmacological consequences of long\u2010term morphine treatment in patients with cancer and chronic non\u2010malignant pain"],"prefix":"10.1002","volume":"8","author":[{"given":"Gertrud","family":"Andersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Sj\u00f8gren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen Honor\u00e9","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels\u2010Henrik","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lona","family":"Christrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(97)00020-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/63.4.380"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0885-3924(95)00148-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)90088-4"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-199611000-00027"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/64.5.547"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(194811)1:4<634::AID-CNCR2820010410>3.0.CO;2-L"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-6576.2003.00138.x"},{"key":"e_1_2_7_11_1","first-page":"335","volume-title":"Experimental pharmacology","author":"McQuay H","year":"1997"},{"key":"e_1_2_7_12_1","unstructured":"MikusG VonRichterO HofmannU EichelbaumM Fischer\u2010BoschM.Glucuronidation of morphine in human liver and small intestine. 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