TABLE 3.
Pharmacokinetic parameters stratified by CYP2D6 genotype.
| CYP2D6 activity (semi-quantitative gene dosage) a | ||||||||
|---|---|---|---|---|---|---|---|---|
| Parameter | 0 (n = 3) | 0.5 (n = 2) | 1 (n = 10) | 1.5 (n = 6) | 2 (n = 11) | 2.5 (n = 1) | 3 (n = 2) | p-value b |
| Amitriptyline | ||||||||
| t1/2 (h) | 23.7 | 24.2 | 21.4 | 19.8 | 19.5 | 14.0 | 20.6 | 0.046 |
| Tmax (h) | 3.4 | 2.0 | 2.7 | 3.7 | 3.4 | 6.0 | 2.0 | 0.677 |
| Cmax (µg/L) | 10.9 | 12.7 | 11.9 | 10.3 | 10.0 | 7.0 | 10.2 | 0.243 |
| AUCinf (h*µg/L) | 310.6 | 214.4 | 250.8 | 225.6 | 195.5 | 157.7 | 157.0 | 0.011 |
| AUC48h (h*µg/L) | 236.2 | 165.9 | 198.8 | 183.9 | 162.2 | 141.5 | 130.0 | 0.037 |
| CL (L/min) | 1.45 | 2.09 | 1.81 | 2.03 | 2.25 | 2.64 | 2.92 | 0.011 |
| Vz (L) | 2,982 | 4,189 | 3,269 | 3,446 | 3,768 | 3,192 | 5,361 | 0.269 |
| Nortriptyline | ||||||||
| t1/2 (h) | 92.0 c | 105.1 | 64.2 | 51.9 | 29.9 c | 25.0 | 26.9 | < 0.001 |
| Tmax (h) | 18.9 | 15.5 | 6.2 | 7.0 | 7.7 | 6.0 | 6.0 | 0.074 |
| Cmax (µg/L) | 3.48 | 5.54 | 2.94 | 2.79 | 2.57 | 3.11 | 2.49 | 0.019 |
| AUC48h (h*µg/L) | 144.6 | 222.2 | 103.8 | 98.3 | 81.8 | 89.1 | 71.1 | 0.001 |
Data are shown as the mean. The study population was not selected based on their CYP2D6 genotypes.
a
The genotype-based CYP2D6 activity is based on the semi-quantitative gene dosage, as described earlier (Steimer et al., 2004).
b
Differences were analysed for statistical significance using the Jonckheere-Terpstra test. Significant values are highlighted in bold.
c
In 2 subjects carrying zero active CYP2D6 alleles and in one subjects with a CYP2D6 gene activity of 2, no decrease in NT concentration was observed and, therefore, no terminal elimination rate could be calculated.