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Routine drug monitoring of serum concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide do not predict clinical observations in cancer patients

Department of Anaesthesia and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway and Unit for Applied Clinical Research, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Petter C Borchgrevink

Ola Dale

Department of Anaesthesia and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway

Kolbjørn Zahlsen

Trond Aamo

Department of Clinical Pharmacology, St Olavs University Hospital, Trondheim, Norway

Peter Fayers

Unit for Applied Clinical Research, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway and the Department of Public Health, University of Aberdeen, Aberdeen, UK

Bjørn Fougner

Unit for Applied Clinical Research, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Stein Kaasa

Unit for Applied Clinical Research, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway and Palliative Medicine Unit, Department of Oncology, St Olavs University Hospital, Trondheim, Norway

The clinical importance of routine drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. We measured morphine, M6G and M3G serum concentrations in cancer pain patients receiving oral (n = 263, median dose 80 mg/24 hours) or subcutaneous (sc) (n = 35, median dose 110 mg/24 hours) morphine. Regression analyses were performed to investigate if serum concentrations of morphine, M3G and M6G predicted pain intensity (Brief Pain Inventory), health-related quality-of-life variables (EORTC QLQ-C30) and cognitive function (Mini-Mental Score). Serum concentrations were also compared in patients categorized as morphine ’treatment successesfland ‘treatment failures’.

We observed that serum concentrations of morphine, M6G or M3G did not predict pain intensity, cognitive function, nausea or tiredness. ‘Treatment failuresflcaused by nausea, tiredness, cognitive failure or constipation did not have statistically significant different morphine, M6G and M3G serum concentrations than patients classified as ’treatment successes’.

In conclusion, this study did not observe any concentration–effect relationships of morphine, M3G or M6G with pain intensity, nausea, constipation, tiredness or cognitive failure in blood samples obtained during routine clinical drug monitoring in cancer patients. This result suggests that therapeutic drug monitoring as a routine tool during chronic morphine treatment has limited value for clinical decision making.

Key Words: cancer • drug monitoring • morphine • morphine-3-glucuronide • morphine-6-glucuronide

Palliative Medicine, Vol. 17, No. 8, 679-687 (2003)
DOI: 10.1191/0269216303pm835oa


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