Serum concentrations of tramadol enantiomers during patient-controlled analgesia

Aims Tramadol, a centrally acting analgesic, is used as a racemate, contain ing 50% of a (+)- and 50% of a (-)-enantiomer. This paper presents the phar macokinetic results of postoperative patient-controlled analgesia using (+) -tranladol, (-)-tramadol or the racemate. Methods Ninety-eight patients recovering from major gynaecological surgery were treated in a 1-randomised, double-blind study with (+)-tramadol, (-)-t ramadol or the racemate. Following an i.v. bolus up to a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. Prior to each demand, the serum concentrations of the enantiomer s of tramadol and its metabolite M1 were measured in 92 patients. Results The mean concentrations of tramadol during the postsurgery phase we re 470+/-323 ng ml(-1), 590+/-110ng ml(-1) and 771+/-451 ng ml(-1) in the ( +)-, racemate- and (-)-group, respectively ((+) vs (-), P<0.05); the mean c oncentrations of the metabolite M1 were 57+/-18 ng ml(-1), 84+/-34 ng ml(-1 ) and 96+/-41 ng ml(-1) in the (+)-, racemate- and (-)-group, respectively ((+) vs (-) and (+) vs racemate, P<0.05). The mean concentrations of (+)-tr amadol and (+)-M1 were lower in the racemate- than in the (+)-group (P<0.05 ), those of (-)-tramadol and (-)-M1 were lower in the racemate than in the (-)-group (P<0.05). In the racemate group, the mean serum concentrations of (+)-tramadol were higher than those of (-)-tramadol (P<0.05), whereas the mean serum concentrations of (-)-M1 were higher than those of (+)-M1 (P< 0. 05). Conclusions The therapeutic serum concentration of tramadol and M1 showed a great variability. The lowest mean concentrations were measured in the (+) -group and the highest in (-)-group. This is in agreement with the clinical finding that (+)-tramadol is a more potent analgesic than (-)-tramadol.