TABLE 2.
Impact of CYP2C19 and CYP2B6 genotype on sertraline concentration estimated in the fixed effect mixed‐model analysis
| Phenotype | Genotype | Patients, n (%) | Samples, n | Sertraline | ||
|---|---|---|---|---|---|---|
| Predicted mean serum concentration, nM/100 mg day | Fold difference | p‐Value | ||||
| CYP2C19 | ||||||
| NM | CYP2C19*1/*1 (Ref.) | 160 (19.1) | 288 | 71.6 (62.5–82.13) | ‐ | ‐ |
| UM | CYP2C19*17/CYP2C19*17 | 44 (5.2) | 89 | 56.2 (47.8–66.0) | 0.78 (0.67–0.92) | 0.003 |
| CYP2C:TG/CYP2C:TG | 26 (3.1) | 34 | 56.5 (46.1–69.2) | 0.79 (0.64–0.97) | 0.022 | |
| CYP2C:TG/CYP2C19*17 | 65 (7.7) | 108 | 57.3 (49.4–66.4) | 0.80 (0.69–0.93) | 0.003 | |
| RM | CYP2C19*1/CYP2C19*17 | 150 (17.9) | 286 | 59.5 (53.3–66.4) | 0.83 (0.74–0.93) | <0.001 |
| CYP2C19*1/ CYP2C:TG | 142 (16.9) | 222 | 72.2 (64.5–80.8) | 1.01 (0.90–1.13) | 0.893 | |
| IM | CYP2C19*17/CYP2C19 Null | 55 (6.6) | 93 | 74.1 (63.8–86.1) | 1.03 (0.89–1.20) | 0.661 |
| CYP2C:TG/CYP2C19 Null | 61 (7.3) | 120 | 86.6 (75.0–100.0) | 1.21 (1.05–1.40) | 0.010 | |
| CYP2C19*1/CYP2C19 Null | 108 (12.9) | 167 | 97.8 (86.8–110.3) | 1.37 (1.21–1.54) | <0.001 | |
| PM | CYP2C19Null/CYP2C19 Null | 29 (3.5) | 75 | 163.3 (134.6–198.1) | 2.28 (1.88–2.77) | <0.001 |
| CYP2B6 | ||||||
| NM | CYP2B6*1/*1 (Ref.) | 454 (57.3) | 848 | 71.6 (62.5–82.1) | ‐ | ‐ |
| UM | CYP2B6 (*1/*4, *4/*4) | 37 (4.7) | 70 | 59.2 (50.2–69.7) | 0.83 (0.70–0.97) | 0.022 |
| IM | CYP2B6 (*1/*6, *1/*9, *4/*6) | 261 (33.0) | 403 | 82.3 (76.5–88.5) | 1.15 (1.07–1.24) | <0.001 |
| PM | CYP2B6 (*6/*6, *9/*9) | 40 (5.1) | 48 | 89.4 (75.9–105.3) | 1.25 (1.06–1.47) | 0.008 |
Note: A 1.9‐fold difference (p = 0.019) and a 1.18‐fold difference (p < 0.001) in sertraline concentration were observed for women and patients aged >65 years, respectively.
Null = no function allele (i.e. the presence of CYP2C19*2, CYP2C19*3, or CYP2C19*4).
Ref. = reference genotype.
Genotype is used as fixed effects in the mixed model. The sertraline concentration of patients not carrying any of the analyzed variants of CYP2C19 or CYP2B6 were set as the reference group. Fold difference represents the estimated relative impact of the occurrence of the genotype on sertraline concentration, as compared with the reference group. Serum concentrations are predicted from the mixed‐model analysis, with age <65 years and sampling time 20 h as model determined covariate values.
Abbreviations: CI, confidence interval; IM, intermediate metabolizer; NM, normal metabolizer; PM, poor metabolizer; RM, rapid metabolizer; UM, ultrarapid metabolizer.