Table 1.
In Vitro Assessment of Cytochrome P450 Inhibition by Tenapanor With Model Substrates
| CYP | Substrate, Concentration | Metabolite | Tenapanor IC50, μM (n = 3) |
|---|---|---|---|
| 1A2 | phenacetin, 30 μM | paracetamol | NI |
| 2B6 | bupropion, 80 μM | hydroxybupropion | 15.4 ± 7.5 |
| 2C8 | amodiaquine, 2 μM | desethylamodiaquine | 10.4 ± 3.0 |
| 2C9 | diclofenac, 10 μM | 4‐OH‐diclofenac | 14.2 ± 3.2 |
| 2C19 | S‐mephenytoin, 35 μM | 4‐OH‐mephenytoin | >30a (32.9 ± 1.9%) |
| 2D6 | bufuralol, 5 μM | 1‐OH‐bufuralol | 3.26 ± 0.54 |
| 3A4/5 | midazolam, 3 μM | 1‐OH‐midazolam | 0.402 ± 0.032 |
| 3A4/5 | nifedipine, 25 μM | oxidized nifedipine | 0.680 ± 0.157 |
CYP, cytochrome P450; IC50, half‐maximal inhibitory concentration; NI, no inhibition detected.
Data are presented as mean ± SD.
a
Statistically significant (P < .05) inhibition was observed at the highest concentration.