Summary of unbound plasma concentration of probenecid and pyrimethamine and their inhibitory potential for 6β-OHF–related transporters and enzymes
| Probenecid (Iu 12.2±0.9 − 41.6±3.0 µM) | Pyrimethamine (Iu ∼300 nM) | |||||
|---|---|---|---|---|---|---|
| Transporter/enzyme | Substrate | Ki | Reference | Substrate | Ki or IC50 (μM) | Reference |
| μM | μM | |||||
| OAT3 | 6β-OHF | 12.1 ± 3.8 | Imamura et al., 2013 | 6β-OHF | 32.0 ± 6.2a | Present study |
| Estrone-3-sulfate | 4.9 ± 1.4 | Khamdang et al., 2004 | ||||
| Fexofenadine | 1.3 ± 0.3 | Tahara et al., 2006 | ||||
| OCT2 | Cimetidine | >1000 | Tahara et al., 2005 | TEA | 10 ± 1 | Ito et al., 2010 |
| Famotidine | >1000 | Tahara et al., 2005 | ||||
| MATE1 | 6β-OHF | >300 | Present study | 6β-OHF | 0.281 ± 0.033 | Imamura et al., 2013 |
| TEA | 0.077 ± 0.013 | Ito et al., 2010 | ||||
| MATE2-K | Not tested | TEA | 0.046 ± 0.006 | Ito et al., 2010 | ||
| CYP3A4 | Midazolam | >100 | Present study | Midazolam | >100a | Present study |
| 11β-HSD2 | Cortisol | >300 | Present study | Cortisol | >300a | Present study |
Iu, maximum unbound plasma concentration.
↵a Representing IC50 value.