Table 4.
Comparison of predicted and observed gene–drug–drug interaction trials
| Substrate | Inhibitor | CYP2D6 genotype | n | AUCR | AUCRx/AUCRy | Reference study | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Predicted | Observed | R pred/obs | Compared genotypes | Predicted | Observed | R pred/obs | |||||
| Dextromethorphan | Duloxetine | AS1 | 17 | 2.6 (2.5–2.7) | 1.8 (1.5–2.1) | 1.43 | x = AS2 | 1.28 | 1.33 | 0.96 | Ref. 10 |
| AS2 | 16 | 3.3 (3.2–3.4) | 2.4 (1.8–3.2) | 1.38 | y = AS1 | ||||||
| Paroxetine | AS1 | 17 | 4.7 (4.4–5.0) | 8.5 (6.7–10.8) | 0.56 | x = AS2 | 1.22 | 1.72 | 0.71 | ||
| AS2 | 16 | 5.8 (5.3–6.3) | 14.6 (10.0–21.4) | 0.40 | y = AS1 | ||||||
| Tolterodine | Fluoxetine | AS0 | 2 | 1.3 (1.3–1.40) | 1.25 | 1.06 | x = AS1 | 2.62 | 4.38 | 0.60 | Ref. 29 |
| AS1 | 4 | 3.4 (3.1–3.8) | 5.47 | 0.62 | y = AS0 | ||||||
| x = AS2 | 2.38 | 3.18 | 0.75 | ||||||||
| AS2 | 3 | 8.1 (7.4–8.9) | 17.4 | 0.47 | y = AS1 | ||||||
| Risperidone | Fluoxetine | PM | 2 | 1.4 (1.3–1.5) | 1.3 | 1.06 | x = EM | 2.12 | 3.22 | 0.66 | Ref. 50 |
| EM | 7 | 2.9 (2.7–3.1) | 4.2 | 0.70 | y = PM | ||||||
AS0, activity score 0; AS1, activity score 1; AS2, activity score 2; AUCR, ratio of the substrate area under the concentration‐time curve in the presence and absence of the inhibitor; AUCRx/AUCRy, ratio of AUCR in genotype x versus genotype y; CYP2D6, cytochrome P450 2D6; EM, extensive metabolizer; PM, poor metabolizer; R pred/obs, ratio of model‐predicted mean exposure change of substrate to observed value.