Table 3.
Inhibition of urate transporters by drugs with a clinically observed uricosuric effect. Interactions were predicted to be clinically significant based on the following cut-off values: for intestinal BCRP, R = 1 + Cgut/(IC50 or Ki) ≥ 11 (shown in bold); for renal transporters, Cmax,u/(IC50 or Ki) ≥ 0.02 (shown in bold only) or ≥0.1 (shown in bold and underlined). Values in red were obtained using urate as a probe substrate. For each drug/transporter pair, results from different studies are separated by semicolons. All values are in µM. Abbreviations: Secr., secretion; Reabs., reabsorption; N/I, no inhibition; (H)/(L), high/low affinity transport. 1 Fenofibrate prodrug is present in the gut only; the effective species in the kidney is fenofibric acid.
| Transporter | BCRP (Gut) | OAT1 | OAT3 | BCRP (Kidney) | MRP4 | NPT1 | NPT4 | URAT1 | OAT4 | OAT10 | GLUT9 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Role | Secr. | Secr. | Secr. | Secr. | Secr. | Secr. | Secr. | Reabs. | Reabs. | Reabs. | Reabs. | |
| Drug/Compound | References | |||||||||||
| Benzbromarone | IC50 = 0.289 | Ki = 0.22; IC50 = 12.75; 13.23; 3.14 | Ki = 0.11; IC50 = 0.967 | IC50 = 0.289 | IC50 = 0.104(H)/15.6 (L) | IC50: 17.1 | Ki = 0.052; IC50 =0.18;0.29 | IC50 = 3.19 | IC50 > 3 | IC50 ~ 100 | [68,69,71,94,105,118,119] | |
| Probenecid | IC50 = 433 | IC50 = 49.68; 4.66; 10.9 | IC50 = 27.9; 2.37 | IC50 = 132 (potentia-tion) | IC50 = 66.82; 13.23, 165 | IC50 = 15.54 | [69,70,71,94,118] | |||||
| Lesinurad | IC50 > 3000; 26.4; >100 | IC50 = 43.99; 4.3; 6.99 | IC50 = 1.07; 3.5 | IC50 > 3000; 26.4; >100 | IC50 = 65.47; 3.53 | IC50 = 2.03 | IC50 > 100 | [69,94,95,118] | ||||
| Verinurad | IC50 = 4.6 | IC50 = 0.025 | IC50 = 5.9 | [120] | ||||||||
| Dotinurad | IC50 = 4.16 | IC50 = 4.08 | IC50 = 1.32 | IC50 = 4.16 | IC50 = 0.0372 | [69] | ||||||
| Arhalofenate | IC50 = 92 | IC50 = 2.6 | IC50 = 53 | [119] | ||||||||
| Fenofibrate/Fenofibric acid 1 | IC50 = 170 | Ki = 2.2 | IC50 = 35.68 | [98,121,122] | ||||||||
| Tranilast | N/I | complete inh at 100 | IC50 = ~15 | N/I | IC50 = 18.9 | IC50 = ~21; Ki = 21.33 | IC50 = ~22 | IC50 = ~31 | (GLUT9a) IC50 = 15.6; Ki = 17.13 | [68] | ||
| Losartan | N/I | IC50 = 12 | IC50 = 1.6 | N/I | IC50 = 1.5 | Ki = 0.0077 | IC50 = 18 | IC50 = ~1000 (mSlc2a9) | [74,101,123] | |||
| Sulfinpyrazone | IC50 = 0.16(H)/40 (L) | IC50 = 716; 3.4 | [71,120,124] | |||||||||
| Salicylate (high dose) | IC50 = 1573.4; Ki = 341 | IC50 = 2.1 (H)/1547 (L) | IC50 = 106; 23.9 | [34,71,75,104,125] | ||||||||
| Epaminurad | Ki = 7.2 | Ki = 2.4 | Ki = 0.057 | [105] |