TABLE 4

Simulated and observed atomoxetine PK in different ethnic populations

Atomoxetine disposition in Chinese and Japanese subjects was simulated using the different models in Simcyp as described in Materials and Methods. Bold values are outside the acceptance range.

CYP2D6 Status	Observed Value (Acceptance Range)^{^a}	Simulated Asian Population^{^a}	Simulated Caucasian Population^{^a}
AUC (μghr/mL*)
Chinese study 40 mg single dose^{^b}
EM	2.24 (1.28–3.97)	3.53	1.95
CYP2D610/10 (IM)	4.96 (2.82–8.78)	7.62
CYP2D610/10 adjusted^{^b}		18.2	8.10
Chinese study 80 mg every day for 7 days
EM	4.43 (2.52–7.84)	7.06	3.36
CYP2D610/10 (IM)	9.69 (5.53–17.2)	16.3
CYP2D610/10 adjusted^{^b}		35.8	16.3
Japanese study 10 mg single dose^{^c}
EM	0.44 (0.25–0.78)	0.93	0.38
CYP2D610/10 (IM)	0.71 (0.41–1.26)	2.13
CYP2D610/10 adjusted^{^b}		6.80	2.03
Japanese study 120 mg single dose^{^c}
EM	5.26 (3.00–9.31)	11.2	4.65
CYP2D610/10 (IM)	9.8 (5.59–17.3)	25.5
CYP2D610/10 adjusted^{^b}		81.7	24.0

C_max (ng/mL)
Chinese study 40 mg single dose
EM	360 (247–472)	480	343
CYP2D610/10 (IM)	530 (403–694)	600
CYP2D610/10 adjusted^{^b}		709	543
Chinese study 80 mg every day for 7 days
EM	815 (619–1068)	1079	651
CYP2D610/10 (IM)	1199 (911–1571)	1499
CYP2D610/10 adjusted^{^b}		2319	1379
Japanese study 10 mg single dose^{^d}
EM	102 (77.2–133)	124	86
CYP2D610/10 (IM)	125 (95.1–164)	160
CYP2D610/10 adjusted^{^b}		181	136
Japanese study 120 mg single dose^{^d}
EM	978 (743–1281)	1490	860
CYP2D610/10 (IM)	1271 (966–1665)	1880
CYP2D610/10 adjusted^{^b}		2178	1630

IM, intermediate metabolizer.
↵^a Geometric mean.
↵^b The CL_int value for atomoxetine was adjusted based on in vitro data as discussed in Materials and Methods.
↵^c Trial B4Z-LE-LYAN; the AUC values are given (μg⋅h/ml) (Center for Drug Evaluation and Research, 2002).
↵^d Trial B4Z-LE-LYAN; the C_max values are given (ng/ml) (Center for Drug Evaluation and Research, 2002).