Table 1.
Summary of age and genotype effects for drugs considered to be affected in a relevant manner by genomic variation
| Drug | Enzyme/transporter | Age PK ratio (systemic exposure in elderly/young) | Genotype PK ratio (slowest metabolizer/ normal metabolizer) | Ultrarapid genotype PK ratio (fastest metabolizer/normal metabolizer) |
|---|---|---|---|---|
| Acenocoumarol, (R) enantiomer | CYP2C9 | 0.99 | ||
| Amitriptyline | CYP2C19 | 1.16 | 1.51 | 0.75 |
| Amitriptyline | CYP2D6 | 1.16 | 1.69 | 0.82 |
| Aripiprazole | CYP2D6 | 1.25 | 1.75 | 0.83 |
| Atazanavir | CYP3A5 | 0.88 | 1.03 | |
| Atazanavir | UGT1A1 | 0.88 | a1.03 | |
| Atomoxetine | CYP2D6 | 9.07 | ||
| Atorvastatin | OATP1B1 | 1.34 | 1.82 | |
| Azathioprine | TPMT | 17.01 | ||
| Brexpiprazole | CYP2D6 | 1.05 | 4.28 | |
| Brivartaracetam | CYP2C19 | 1.15 | 1.42 | |
| Capecitabine | DPD | 3.48 | b10.00 | |
| Celecoxib | CYP2C9 | 1.49 | 3.34 | |
| Ciclosporin | CYP3A4 | 1.32 | 1.56 | |
| Citalopram | CYP2C19 | 1.71 | 1.82 | 0.83 |
| Clobazam | CYP2C19 | 1.47 | 7.39 | |
| Clomipramine | CYP2D6 | 2.56 | 2.17 | 0.79 |
| Clomipramine | CYP2C19 | 2.56 | 1.54 | 0.85 |
| Clopidogrel | CYP2C19 | 1.44 | 0.73 | |
| Clozapine | CYP2C19 | 0.92 | 1.69 | 0.88 |
| Codeine | CYP2D6 | d2.59 | d0.05 | d1.45 |
| Darifenacin | CYP2D6 | 1.23 | 1.70 | |
| Desipramine | CYP2D6 | 1.32 | 5.41 | 0.65 |
| Desmethyldiazepam | CYP2C19 | 2.63 | 2.37 | |
| Dexlansoprazole | CYP2C19 | 1.35 | 4.61 | |
| Dextromethorphan | CYP2D6 | 1.49 | ||
| Diazepam | CYP2C19 | 1.12 | 1.48 | |
| Dihydrocodeine | CYP2D6 | 1.85 | 1.12 | |
| Dolasetron | CYP2D6 | 1.31 | 2.00 | |
| Dolutegravir | UGT1A1 | 0.86 | 1.46 | |
| Doxepin | CYP2D6 | 1.91 | 3.87 | 0.65 |
| Dronabinol | CYP2C9 | 3.09 | ||
| Duloxetine | CYP2D6 | 1.24 | 1.65 | 0.84 |
| Efavirenz | CYP2B6 | 1.05 | 3.11 | |
| Eliglustat | CYP2D6 | 7.00 | ||
| Endoxifen | CYP2D6 | 1.23 | 0.40 | |
| Escitalopram | CYP2C19 | 1.23 | 1.74 | 0.68 |
| Esomeprazole | CYP2C19 | 1.58 | ||
| Etoposide | UGT1A1 | 1.28 | 1.06 | |
| Ezetemibe | UGT1A1 | 2.11 | 1.77 | |
| Fesoterodine | CYP2D6 | 1.00 | 2.31 | |
| Flecainide | CYP2D6 | 1.29 | 1.28 | |
| Flibanserin | CYP2C9 | 0.64 | 1.30 | |
| Fluorouracil | DPD | 1.12 | 10.00 | |
| Fluoxetine | CYP2D6 | 0.88 | 3.61 | |
| Fluoxetine, (R) enantiomer | CYP2C9 | 1.86 | ||
| Fluoxetine, (S) enantiomer | CYP2D6 | 1.37 | 0.74 | |
| Flurbiprofen | CYP2C9 | 1.21 | 1.63 | |
| Fluvastatin | CYP2C9 | 1.11 | 2.13 | |
| Fluvoxamine | CYP2D6 | 2.91 | 1.73 | 0.8 |
| Galantamine | CYP2D6 | 1.38 | 1.33 | |
| Glibenclamide | CYP2C9 | 0.74 | 1.69 | |
| Glimepiride | CYP2C9 | 1.48 | ||
| Glipizide | CYP2C9 | 0.90 | 5.45 | |
| Haloperidol | CYP2D6 | 1.23 | 1.86 | 1.1 |
| Hydralazine | NAT2 | 1.22 | 2.25 | |
| Ibuprofen | CYP2C9 | 0.99 | 1.81 | |
| Ibuprofen, (S) enantiomer | CYP2C9 | 1.26 | ||
| Imipramine | CYP2D6 | 1.86 | 4.70 | 0.72 |
| Irinotecan | UGT1A1 | 1.31 | c1.61 | |
| Isoniazid | NAT2 | 1.55 | 2.49 | |
| Lansoprazole | CYP2C19 | 1.50 | 4.91 | |
| Lesinurad | CYP2C9 | 1.96 | ||
| Lorazepam | UGT2B15 | 1.29 | 1.72 | |
| Losartan | CYP2C9 | 1.35 | ||
| Mercaptopurine | TPMT | 2.09 | ||
| Methadone, (R) enantiomer | CYP2B6 | 1.83 | ||
| Metoprolol | CYP2D6 | 1.17 | 2.28 | 0.43 |
| Morphine | OCT1 | 1.57 | 1.70 | |
| Nateglinide | CYP2C9 | 1.35 | ||
| Nilotinib | UGT1A1 | a | ||
| Nortriptyline | CYP2D6 | 1.63 | 3.32 | 0.66 |
| Olanzapine | CYP2D6 | 1.32 | 2.00 | |
| Omeprazole | CYP2C19 | 1.99 | 8.83 | |
| Ondansetron | CYP2D6 | 1.42 | 1.04 | |
| Ondansetron | OCT1 | 1.42 | 3.00 | |
| Oxazepam | UGT2B15 | 1.48 | 2.08 | |
| Oxycodone | CYP2D6 | 1.55 | ||
| Pantoprazole | CYP2C19 | 1.39 | 5.06 | 0.67 |
| Paroxetine | CYP2D6 | 3.82 | 2.45 | 0.74 |
| Pazopanib | UGT1A1 | a | ||
| Perphenazine | CYP2D6 | 2.58 | 0.71 | |
| Phenytoin | CYP2C9 | 1.34 | 1.55 | |
| Pimozide | CYP2D6 | 2.00 | 0.4 | |
| Piroxicam | CYP2C9 | 0.98 | 1.67 | |
| Pitavastatin | OATP1B1 | 2.62 | ||
| Pravastatin | OATP1B1 | 1.48 | 1.92 | |
| Propafenone | CYP2D6 | 3.77 | ||
| Propafenone, (R) enantiomer | CYP2D6 | |||
| Rabeprazole | CYP2C19 | 1.88 | 3.60 | |
| Risperidone | CYP2D6 | 2.08 | 6.85 | 0.47 |
| Rosuvastatin | OATP1B1 | 0.87 | 1.72 | |
| Sertraline | CYP2C19 | 1.06 | 1.92 | 0.92 |
| Simvastatin | OATP1B1 | 1.45 | 2.62 | |
| Sirolimus | CYP3A4 | 2.49 | ||
| Sumatriptan | OCT1 | 2.15 | ||
| Tacrolimus | CYP3A5 | 1.64 | 2.10 | |
| Tenoxicam | CYP2C9 | 1.02 | 1.59 | |
| Theophylline | CYP1A2 | 1.31 | ||
| Thioridazine | CYP2D6 | 2.59 | 2.98 | 0.81 |
| Timolol | CYP2D6 | 1.67 | 0.66 | |
| Tolbutamide | CYP2C9 | 4.77 | ||
| Tolterodine | CYP2D6 | 1.29 | 4.77 | |
| Torsemide | OATP1B1 | 1.50 | ||
| Tramadol, (+) enantiomer | CYP2D6 | 1.09 | 3.02 | 0.85 |
| Trimipramine | CYP2D6 | 1.99 | 0.8 | |
| Tropisetron | OCT1 | 2.00 | ||
| Tropisetron | CYP2D6 | 2.89 | 0.84 | |
| Venlafaxine | CYP2D6 | 2.31 | 1.41 | 0.63 |
| Voriconazole | CYP2C19 | 1.61 | 2.78 | 0.81 |
| Vorinostat | UGT2B17 | 1.25 | ||
| Vortioxetine | CYP2D6 | 1.32 | ||
| Warfarin | CYP2C9 | 1.34 | 1.94 | |
| Warfarin, (S) enantiomer | CYP2C9 | 1.35 | 3.60 | |
| Zolpidem | CYP3A4 | 2.18 | ||
| Zopiclone | CYP3A4 | 1.68 | ||
| Zopiclone, (S) enantiomer | CYP3A4 | 1.57 | ||
| Zuclopenthixol | CYP2D6 | 2.05 | 0.8 |
Age PK ratios reflect the effect of old age on drug exposure (calculated as AUC or trough concentration in elderly over the same parameter in the young). Genotype PK ratios reflect the increase in systemic drug exposure in poor metabolizers relative to normal metabolizers. The ultrarapid genotype PK ratio is the ratio of drug exposure in ultrarapid metabolizers over normal metabolizers; ultrarapid genotypes are only known for some drug metabolizing enzymes.
a
No known PK difference but drug induced hyperbilirubinemia dependent on UGT1A1 genotype.
b
Estimated for 5‐fluorouracil.
c
Genotype data for active metabolite SN38.
d
In age studies measurement of codeine, in genotype studies measurement of morphine.