caa a22 4500 475817893 CHVBK 20180406123814.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s002280050003 doi (NATIONALLICENCE)springer-10.1007/s002280050003 Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine [Elektronische Daten] [P. Klepstad, S. Kaasa, P. C. Borchgrevink] Objective: To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients. Methods: Forty patients with malignant disease and intolerable pain on weak opioids (codeine/dextropropoxyphen) were included. After a wash-out period, titration with immediate-release (IR) morphine was started. When a stable dose was achieved, the morphine treatment was changed to slow-release (SR) morphine in equivalent daily dosages. Clinical data and serum concentrations of morphine, M3G and M6G were obtained at the end of the IR and SR morphine treatment periods. Results: The mean trough serum morphine concentration associated with pain relief was 66 nmol/l. The corresponding mean concentrations of M6G and M3G were 257 nmol/l and 1943 nmol/l, respectively. Morphine serum trough concentrations showed a 33-fold variation. Seventy percent of the variation was predicted in a model including age, daily morphine dose and M6G/morphine ratio as independent variables. No associations were observed between side effects and serum concentrations of morphine and its metabolites. Conclusion: In this study, a mean serum trough morphine concentration of 66 nmol/l was associated with satisfactory pain relief when disease progression required an increase in intensity of pain therapy from step II to step III in the World Health Organization pain ladder. An increased ratio of M6G to morphine serum concentrations predicted lower effective serum morphine concentrations at the time of satisfactory pain relief. This observation supports that M6G contributes to the pain control produced by oral morphine in patients with pain caused by malignant disease. Springer-Verlag Berlin Heidelberg, 2000 Key words Pain nationallicence Cancer nationallicence Morphine metabolites nationallicence Klepstad P. Department of Anaesthesiology, University Hospital of Trondheim, Norwegian University of Science and Technology, Trondheim N-7006, Norway e-mail: pklepsta@online.no Tel.: +47-738 68108; Fax: +47-738 68117, NO aut Kaasa S. Unit for Applied Clinical Research, Norwegian University of Science and Technology, Trondheim, Norway, NO aut Borchgrevink P. C. Department of Anaesthesiology, University Hospital of Trondheim, Norwegian University of Science and Technology, Trondheim N-7006, Norway e-mail: pklepsta@online.no Tel.: +47-738 68108; Fax: +47-738 68117, NO aut https://doi.org/10.1007/s002280050003 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050003 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Klepstad P. Department of Anaesthesiology, University Hospital of Trondheim, Norwegian University of Science and Technology, Trondheim N-7006, Norway e-mail: pklepsta@online.no Tel.: +47-738 68108; Fax: +47-738 68117, NO aut NATIONALLICENCE 700 1- Kaasa S. Unit for Applied Clinical Research, Norwegian University of Science and Technology, Trondheim, Norway, NO aut NATIONALLICENCE 700 1- Borchgrevink P. C. Department of Anaesthesiology, University Hospital of Trondheim, Norwegian University of Science and Technology, Trondheim N-7006, Norway e-mail: pklepsta@online.no Tel.: +47-738 68108; Fax: +47-738 68117, NO aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer