Table 3.
CYP2D6 Activity Score, Plasma Donepezil Concentrations and Dose per Day (n = 86)
|
CYP2D6 Activity Score |
CYP2D6 Predicted Phenotype | CYP2D6 Genotype | N (%) | Plasma Donepezil Concentrations (ng/mL) |
Concentration/Dose (ng/mL/mg/day) | Concentration/Dose/Weight (ng/mL/mg/kg/day) | Dosea (mg/day) | Dose/Weight (mg/kg/day) |
|---|---|---|---|---|---|---|---|---|
| 2 | NMs | *1/*1, *1/*2, *2/*2 | 8 (9) | 66.47 (36.68–82.99) | 6.65 (5.48–7.07) | 0.12 (0.10–0.14) | 10 (6.25–10) | 0.17 (0.11–0.20) |
| 1.5 | NMs | *1/*41, *2/*14B, *2/*41 | 4 (5) | 55.49 (43.69–115.10) | 11.10 (8.74–13.04) | 0.22 (0.19–0.26) | 5 (5–8.75) | 0.11 (0.10–0.18) |
| 1.25 | NMs | *1/*10, *2/*10 | 29 (34) | 35.52 (17.34–62.52) | 6.64 (5.14–9.27) | 0.12 (0.10–0.20) | 5 (2.5–8.75) | 0.10 (0.05–0.14) |
| 1 | IMs | *1/*5, *2/*4, *2/*5 | 6 (7) | 48.49 (23.36–88.99) | 7.63 (5.01–11.21) | 0.17 (0.10–0.22) | 7.5 (2.5–10) | 0.14 (0.06–0.21) |
| 0.75 | IMs | *10/*10 DUP, *10/*41 | 5 (6) | 96.03 (55.80–124.62) | 9.60 (7.63–12.46) | 0.19 (0.11–0.25) | 10 (7.5–10) | 0.20 (0.11–0.21) |
| 0.5 | IMs | *10/*10 | 24 (28) | 55.95 (33.68–86.28) | 8.33 (6.12–10.22) | 0.15 (0.11–0.22) | 7.5 (5–10) | 0.16 (0.09–0.20) |
| 0.25 | IMs | *4/*10, *5/*10 | 10 (12) | 77.71 (41.27–124.90) | 8.96 (6.03–10.58) | 0.16 (0.11–0.20) | 10 (5–17) | 0.18 (0.09–0.38) |
Notes: Data are presented as median (interquartile range) unless otherwise stated. aKruskal Wallis test for differences of CY2D6 activity scores across all groups, p = 0.029.
Abbreviations: DUP, duplication; NMs, normal metabolizers (activity score of 1.25 ≤ x ≤ 2.25); IMs, intermediate metabolizers (activity score of 0 < x < 1.25)