Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects.
OBJECTIVE
To study the stereoselectivity in pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1) in human subjects.


METHODS
Trans-T hydrochloride sustained-release tablets were taken orally by 12 healthy male volunteers. After a multiple dosage schedule, the serum concentrations of (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 were determined in serum by high performance capillary electrophoresis (HPCE).


RESULTS
(+)-Trans-T, (-)-trans-T, (+)-M1 and (-)-M1 in human serum were separated by HPCE. The linear range was 2.5-320 microg/L for the enantiomers of trans-T, and 2.5-50 microg/L for the enantiomers of M1. For the enantiomers of trans-T and M1, the intra-day and inter-day RSD were less than 15 % and 20 %, and the relative recoveries were 94.3 %-106.2 % and 90.4 %-107.8 %, respectively; the limit of quantitation was 1.25 microg/L. The serum concentrations of the enantiomers of trans-T reached a steady state in 12 subjects on d 4 after the initial administration. The steady state serum concentrations of (+)-trans-T were higher than that of (-)-trans-T at every sampling points in the subjects. The differences were significant in the main pharmacokinetic parameters between (+)-trans-T and (-)-trans-T except Tmax. The serum concentrations of (-)-M1 were higher than that of (+)-M1 in most subjects and at most sampling time points. There were significant differences in Cmax and Cmin between the enantiomers of M1.


CONCLUSIONS
The pharmacokinetics of trans-T and M1 was found to be stereoselective. (+)-Trans-T was shown to be absorbed completely, but eliminated more slowly. The pharmacokinetic stereoselectivity of M1 was different among human subjects.
Liu
H C
HC
Department of Clinical Pharmacology, Bethune International Peace Hospital, Shijiazhuang 050082, China. lhcl@sj-user.he.cninfo.net
Liu
T J
TJ
Yang
Y Y
YY
Hou
Y N
YN
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics; D019075:Electrophoresis, Capillary; D006801:Humans; D008297:Male; D013237:Stereoisomerism; D014147:Tramadol / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; C080580:O-demethyltramadol; D014147:Tramadol