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The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite levels
Author(s) -
Sindrup Søren H.,
Madsen Claus,
Brøsen Kim,
Jensen Troels S.
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1053/cp.1999.v66.103171001
Subject(s) - tramadol , medicine , anesthesia , placebo , neuropathic pain , analgesic , opioid , metabolite , pharmacology , alternative medicine , receptor , pathology
Background and Objective Tramadol is a racemic drug that may act through a monoaminergic effect of (+)‐ and (−)‐tramadol and through an opioid effect of its metabolite (+)‐M1. The objective of this study was to investigate the relationship between relief of pain and serum concentrations of tramadol and M1 in tramadol treatment of painful polyneuropathy. Methods In a randomized, double‐blind, placebo‐controlled trial of 200 to 400 mg/day tramadol, serum concentrations of (+)‐ and (−)‐tramadol and (+)‐ and (−)‐M1 were determined in 28 of 34 patients. On‐going and touch‐evoked pain was rated daily by the patients by use of 0‐ to 10‐point numeric rating scales during two 4‐week treatment periods. Results Tramadol significantly reduced both on‐going ( P = .002) and touch‐evoked pain ( P < .001). There was no relation between relief of on‐going and touch‐evoked pain and serum concentrations of (+)‐tramadol, (−)‐tramadol, (+)‐M1, or (−)‐M1 ( P = .11 to P = .89). Seventeen of the patients were categorized as responders for on‐going pain and 16 for touch‐evoked pain. Responders for on‐going pain tended to have higher serum concentrations of (+)‐M1 than nonresponders (median, 27 nmol/L versus 16 nmol/L; P = .08). Isobolograms showed that the fraction of nonresponders was higher among patients with low concentrations of both tramadol and (+)‐M1 both for on‐going ( P = .009) and touch‐evoked ( P = .02) pain. Conclusion The opioid effect of (+)‐M1 may be of importance for tramadol relief of on‐going neuropathic pain but, in general, relief of neuropathic pain seems to depend on both the monoaminergic effect of (+)‐ and (−)‐tramadol and the opioid effect of (+)‐M1. Clinical Pharmacology & Therapeutics (1999) 66 , 636–641; doi: 10.1053/cp.1999.v66.103171001