TABLE 1.
Summary of effect of CYP3A4*22 on pharmacokinetics (PK), dose requirement (DR), toxicity (Tox) or effect (Eff) of the described drugs.
| Drug class | Drug | CYP3A4-guided dosing? | Effect of CYP3A4*22 |
Studies that show |
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| PK | DR | Tox | Eff | Sign. effect | Trends | No effect or opposite effect | |||
| CYP3A4 phenotyping probes | Erythromycin |  |
N-des-methylation activity ↓ | PK: 1 | PK: 0 | PK: 0 | |||
| Midazolam (MDZ) | |
1’-OH-MDZ:MDZ ↓ | PK: 1 | PK: 0 | PK: 0 | ||||
| Immunosuppressants | Tacrolimus | |
C0/D ↑ | D↓ | PK: 9 D: 5 |
PK: 7 D: 0 |
PK: 3 D: 0 |
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| Cyclosporine | |
C0/D ↑ | OR delayed graft function ↑ | PK: 3 D: 1 Tox: 1 |
PK: 0 D: 0 Tox: 1 |
PK: 3 D: 0 Tox: 0 |
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| Sirolimus |  |
In vitro metabolic rate ↓ | PK: 1 | PK: 0 | PK: 0 | ||||
| Everolimus | |
C ↑* | PK: 1 | PK: 1 | PK: 0 | ||||
| Cardiology | Ticagrelor |  |
AUC ↑ | Platelet inhibition ↑ | PK: 1 Eff: 1 |
PK: 0 Eff: 0 |
PK: 0 Eff: 0 |
||
| Sildenafil | |
Cmax/D ↑ | PK: 1 | PK: 0 | PK: 0 | ||||
| Simvastatin | |
C ↑ | D↑ | Total and LDL cholesterol ↑ | PK: 3 D: 1 Eff: 1 |
PK: 1 D: 0 Eff: 0 |
PK: 0 D: 0 Eff: 0 |
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| Atorvastatin | |
2-OH- atorvastatin/atorvastatin AUCinf ↓ | PK: 1 D: 1 |
PK: 1 D: 0 |
PK: 0 D: 0 |
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| Anxiolytics | Alprazolam | |
C:D ↑ | HAMA scale score ↑ | PK: 1 Eff: 1 |
PK: 0 Eff: 0 |
PK: 0 Eff: 0 |
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| Anti-psychotics | Risperidone | |
Cl ↓ | PK: 1 | PK: 2 | PK: 0 | |||
| Pimozide | |
Cl ↓ | PK: 1 | PK: 0 | PK: 0 | ||||
| Quetiapine | |
C/D ↑ | PK: 1 | PK: 0 | PK: 0 | ||||
| Anticancer drugs | Tamoxifen | |
C 4-OH-tam↑ C endoxifen ↑ C tam ↑ | OR hot flash ↓ | PK: 1 Tox: 1 |
PK: 0 Tox: 0 |
PK: 0 Tox: 0 |
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| Exemestane | |
Css ↑ | PK: 1 | PK: 0 | PK: 0 | ||||
| Paclitaxel | |
OR neuro- toxicity↑ | Tox: 1 | Tox: 0 | Tox: 0 | ||||
| Docetaxel | |
OR grade 3-4 toxicity↑ | Tox: 1 | Tox: 0 | Tox: 0 | ||||
| Pazopanib | |
Cl ↓ | D↓ | PK: 1 D: 1 |
PK: 0 D: 0 |
PK: 0 D: 0 |
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| Sunitinib | |
Cl ↓ * | PK: 0 | PK: 1 | PK: 0 | ||||
| Analgesia | Fentanyl | |
Norfentanyl: fentanyl ratio ↓ | PK: 2 | PK: 1 | PK: 0 | |||
| Anti-viral drugs | Lopinavir | |
C0↑ | D↓ | PK: 1 D: 1 |
PK: 0 D: 0 |
PK: 0 D: 0 |
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| Tenofovir alafenamide | |
AUC ↑ | PK: 1 | PK: 0 | PK: 0 | ||||
Third column shows our opinion on the level of evidence considering CYP3A4*22 based dosing in corresponding drug treatment [green: sufficient evidence, orange: more evidence is needed to fully establish clinical value, red: too limited (non-significant) evidence]. Trends are marked with an asterisk (*). AUC, area under the plasma concentration-time curve; C, plasma concentration (not specified); C0, trough concentration; C0/D, dose-adjusted trough concentration; Cl, Clearance; Css, steady-state concentration; D, required dose; OR: odds ratio.