Pharmacokinetics of the enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in healthy male and female chinese volunteers.
By using a high-performance capillary electrophoresis method, the pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1), was studied in healthy male and female Chinese volunteers after oral administration of 100 mg trans-T hydrochloride. The values of Cmax for the enantiomers of trans-T and M1, and AUC0- infinity for (-)-trans T, (+)-M1, and (-)-M1 were higher in females than in males. The values of V(d)/F for the enantiomers of trans-T and CLr for (+)-M1 were lower in females than in males. The value of t(1/2) for (-)-M1 was longer in females than in males. There were significant differences in pharmacokinetic parameters of the two enantiomers of trans-T or M1 both in males and in females. The (+)/(-)-enantiomeric ratios of t(max), V(d)/F for trans-T in males were significantly different from those in females and the (+)/(-)-enantiomeric ratios of pharmacokinetic parameters for M1 in males were similar to those in females. There are gender-related differences in the pharmacokinetics of the enantiomers of trans-T and M1 which may be due to the greater body weights for men and/or the higher CYP2D6 activity in women. The pharmacokinetics of trans-T and M1 is stereoselective in men and women. There is a gender-related difference in the stereoselectivity in pharmacokinetics of trans-T in human and the stereoselectivity in pharmacokinetics of M1 in men is similar to that in women. Chirality 16:112-118, 2004.
Hui-Chen
Liu
L
Department of Clinical Pharmacology, Bethune International Peace Hospital, Shijiazhuang, China. liu-huichen@163.com
Yang
Yu
Y
Na
Wang
W
Ming
Deng
D
Jian-Fang
Liu
L
Hong-Yuan
Xue
X
D000293:Adolescent; D000328:Adult; D044466:Asian People; D001835:Body Weight / Q000187:drug effects; D002681:China; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D013237:Stereoisomerism; D014147:Tramadol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics*
C080580:O-demethyltramadol; D014147:Tramadol