Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele.
OBJECTIVE
To characterize atomoxetine pharmacokinetics, explore the effect of the homozygous CYP2D6*10 genotype on atomoxetine pharmacokinetics and evaluate the tolerability of atomoxetine, in healthy Chinese subjects.


METHODS
Twenty-four subjects, all CYP2D6 extensive metabolizers (EM), were randomized to receive atomoxetine (40 mg qd for 3 days, then 80 mg qd for 7 days) or matching placebo (2 : 1 ratio) in a double-blind fashion. Atomoxetine serum concentrations were measured following single (40 mg) and multiple (80 mg) doses. Adverse events, clinical safety laboratory data and vital signs were assessed during the study.


RESULTS
Atomoxetine was rapidly absorbed with median time to maximum serum concentrations of approximately 1.5 h after single and multiple doses. Atomoxetine concentrations appeared to decrease monoexponentially with a mean apparent terminal half-life (t(1/2)) of approximately 4 h. The apparent clearance, apparent volume of distribution and t(1/2) following single and multiple doses were similar, suggesting linear pharmacokinetics with respect to time. Homozygous CYP2D6*10 subjects had 50% lower clearances compared with other EM subjects, resulting in twofold higher mean exposures. No clinically significant changes or abnormalities were noted in laboratory data and vital signs.


CONCLUSIONS
The pharmacokinetics of atomoxetine in healthy Chinese subjects appears comparable to other ethnic populations. Multiple dosing of 80 mg qd atomoxetine was well tolerated in this study.
Cui
Yi M
YM
Department of Pharmacy, Peking University First Hospital, Beijing, PR China. cuiymzy@126.com
Teng
Choo H
CH
Pan
Alan X
AX
Yuen
Eunice
E
Yeo
Kwee P
KP
Zhou
Ying
Y
Zhao
Xia
X
Long
Amanda J
AJ
Bangs
Mark E
ME
Wise
Stephen D
SD
D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D000069445:Atomoxetine Hydrochloride; D002681:China; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011437:Propylamines / Q000008:administration & dosage / Q000493:pharmacokinetics*
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D019389:Cytochrome P-450 CYP2D6