TABLE 4.
Pharmacokinetic parameters stratified by CYP2C19 genotype.
| CYP2C19 activity score a | |||||||
|---|---|---|---|---|---|---|---|
| Parameter | 0 (n = 1) | 1 (n = 5) | 1.5 (n = 2) | 2 (n = 16) | 2.5 (n = 10) | 3 (n = 1) | p-value b |
| Amitriptyline | |||||||
| t1/2 (h) | 26.7 | 21.6 | 20.3 | 20.1 | 19.8 | 28.3 | 0.359 |
| Tmax (h) | 4.0 | 2.6 | 2.0 | 3.2 | 3.6 | 2.0 | 0.639 |
| Cmax (µg/L) | 11.5 | 11.1 | 16.2 | 10.5 | 9.5 | 13.9 | 0.303 |
| AUCinf (h*µg/L) | 320.9 | 231.0 | 317.0 | 210.0 | 210.7 | 271.0 | 0.254 |
| AUC48h (h*µg/L) | 229.0 | 183.2 | 255.6 | 171.8 | 171.3 | 198.4 | 0.238 |
| CL (L/min) | 1.30 | 1.94 | 1.5 | 2.1 | 2.2 | 1.54 | 0.254 |
| Vz (L) | 3,004 | 3,525 | 2,559 | 3,696 | 3,740 | 3,762 | 0.340 |
| Nortriptyline c | |||||||
| t1/2 (h) | 106.3 | 48.2 | 25.1 | 47.7 | 44.1 | 145 | 0.983 |
| Tmax (h) | 6.0 | 6.0 | 14.1 | 6.6 | 9.9 | 24.9 | 0.452 |
| Cmax (µg/L) | 1.05 | 2.1 | 3.5 | 3.0 | 3.1 | 6.5 | 0.012 |
| AUC48h (h*µg/L) | 39.3 | 69.4 | 123 | 102.8 | 107.8 | 283.7 | 0.008 |
Data are shown as the mean. The study population was not selected based on their CYP2C19 genotypes.
a
For calculating the CYP2C19 activity score, CYP2C19*2 was regarded as zero active, CYP2C19*1 was classified as 1, and CYP2C19*17 as 1.5.
b
Differences were analysed for statistical significance using the Jonckheere-Terpstra test. Significant values are highlighted in bold.
c
In two subjects with CYP2C19*1/*17 genotype and in one subject with CYP2C19*1/*1 genotype, no decrease in NT concentration was observed and, therefore, no terminal elimination rate could be calculated.