Wd. Paar et al., POLYMORPHIC CYP2D6 MEDIATES O-DEMETHYLATION OF THE OPIOID ANALGESIC TRAMADOL, European Journal of Clinical Pharmacology, 53(3-4), 1997, pp. 235-239
Objective: This study was designed to investi gate whether the in vivo
metabolism of tramadol was influenced by CYP2D6 polymorphism. Methods
: The extent of tramadol 0- and N-demethylation was calculated by dete
rmining the amounts of tramadol and 0- and N-desmethyltramadol in 24 h
urine after ingestion of a test dose of tramadol. The 0- and N-demeth
ylation rates were calculated by dividing the 24-h urinary excretion a
mount of tramadol by that of O-and N-desmethyltramadol. Volunteers wer
e phenotyped for CYP2D6 polymorphism using sparteine as an in vivo pro
be. Results and conclusion: High correlation was found between tramado
l-O-demethylation and sparteine oxidation in 71 extensive metabolizers
of sparteine (r(s) = 0.544). The mean metabolic ratio of tramadol O-d
emethylation was significantly higher in poor metabolizers of spartein
e than in extensive metabolizers (4.4 vs 0.8). These in vivo results c
onfirm that tramadol O-demethylation is carried out to a large extent
by the polymorphic CYP2D6.