Effects of the CYP2D6 genotypes on the pharmacokinetics of atomoxetine

We investigated the effect of the CYP2D6 * 10 variant allele on the pharmacokinetics of atomoxetine in 43 healthy Korean subjects. After being genotyped for CYP2D6 using PCR‐RFLP and long‐PCR methods, the subjects were classified into three different genotype groups, CYP2D6 * wt/ * wt (* wt =* 1 or * 2 , n=21), CYP2D6 * wt/ * 10 (n=12) and CYP2D6 * 10/ * 10 (n=10). A single oral dose of 40 mg of atomoxetine was administered to each subject and plasma samples were collected up to 24 hours after atomoxetine administration. C max and AUC values of atomoxetine among the three genotype groups were significantly different. The C max values for atomoxetine in the CYP2D6 * 10/ * 10 and CYP2D6 * wt/ * 10 groups were 1.8‐ and 1.6‐fold higher than in the CYP2D6 * wt/ * wt group, and the AUC inf values for atomoxetine in the CYP2D6 * 10/ * 10 and CYP2D6 * wt/ * 10 groups were 3.5‐ and 2.1‐fold higher than in the CYP2D6 * wt/ * wt group. The AUC inf of atomoxetine in the CYP2D6 * 10/ * 10 group was also significantly higher than in the CYP2D6 * wt/ * 10 group. Differences in the CL/F and t 1/2 of atomoxetine among the three genotype groups were also statistically significant. The CL/F values for atomoxetine in the CYP2D6 * 10/ * 10 and CYP2D6 * wt/ * 10 groups were about 70% and 50% lower than in the CYP2D6 * wt/ * wt group. The mean exposure to atomoxetine is markedly higher in subjects with the CYP2D6 * 10/ * 10 genotype than in those with the CYP2D6 * wt/ * wt genotype.