Analgesic Effects and Assays of Controlled-Release Tramadol and O-Desmethyltramadol in Cancer Patients with Pain

Wojciech      Leppert; Przemyslaw      Mikolajczak

Abstract

Aim of the study: To assess tramadol and O-desmethyltramadol (M1) concentrations and their correlations with analgesia in patients with cancer pain. Patients and methods: Thirty opioid – naive patients with nociceptive pain intensity on VAS (visual analogue scale) > 40 received controlled-release tramadol as the first (15 patients, 7 days) or as the second opioid (15 patients, 7 days). Blood samples were taken on day 2, 4 and 7 at each study period. Tramadol and M1 were assayed by HPLC method. Results: During the first week a trend (p = 0.067) of tramadol level increase was observed in the third comparing to the first assay. In the second week a significant increase of tramadol concentration was observed in the second (p < 0.001) and in the third (p < 0.001) in comparison to the first assay. No significant changes in M1 concentrations were found in the first week. A significant increase of M1 concentration was noted in the second (p < 0.001) and in the third (p < 0.001) assays comparing to the first M1 determination in the second week. Conclusions: A relatively stable tramadol and M1 levels in the first week could be caused by intense tramadol dose titration in the first two days to achieve effective analgesia. The same pattern of tramadol and M1 level increase in the second week indicate their contribution to tramadol analgesia. Few significant correlations were found between tramadol dose, tramadol and M1 serum concentrations with analgesia suggesting the need of individual tramadol dose titration.

Keywords: Analgesia, cancer pain, opioid, tramadol, treatment, O-desmethyltramadol, nociceptive pain, VAS (visual analogue scale), noradrenalin, serotonin, morphine, pethidine, buprenorphine, pentazocine, dihydrocodeine (DHC), opioid-naive patients, paracetamol, metamizol, skin melanoma, myelodysplastic syn-drome, Hodgkin disease, liquid chro-matographic, –, mass spectrometric assay, MRM mode, osteoarthritis, CYP2D6 gene, dihydromorphine, N-demethylation, painful polyneuropathy, enantiomers, dose titration