Table 1a.

Drugs that Increase Urinary Urate Excretion

Drug	Drug Action	Interactions with Urate Transporters (Secretion Pathway)	Interactions with Urate Transporters (Reabsorption Pathway)	Effects on Serum Urate
Primary Uricosuric Agents
Probenecid	Renal tubule reabsorption inhibitor	High affinity inhibitor of OAT1[53] and OAT3[130], lower affinity inhibitor of OAT2[67] and NPT4[58]	Lower affinity inhibitor of URAT1[132] and OAT4[67]	Decreased SU due to decreased urate reabsorption at higher doses Increased SU due to inhibition of secretory transporters
Benzbromarone*	Renal tubule reabsorption inhibitor	OAT1 inhibitor[53]	Inhibitor of SLC2A9 [133] and URAT1[134]	Decreased SU due to increased urinary excretion with decreased urate reabsorption
Sulfinpyrazone	Renal tubule reabsorption inhibitor	---	URAT1 inhibitor [132, 135]
Lesinurad	Renal tubule reabsorption inhibitor	Minimal effects on OAT1 and OAT3[136]	Inhibitor of URAT1 and OAT4[137]
Verinurad†	Renal tubule reabsorption inhibitor	---	URAT1 inhibitor[138]
Dotinurad†	Renal tubule reabsorption inhibitor	---	URAT1 inhibitor[139]
Arhalofenate†	Renal tubule reabsorption inhibitor	---	Inhibitor of URAT1 and OAT4[140]
Agents with Secondary Uricosuric Properties
Tranilast†	Anti-inflammatory with pleiotropic effects	Moderate inhibition of NPT1, OAT1, and OAT3, with no inhibition of ABCG2[141]	High affinity inhibition of URAT1, SLC2A9, OAT4 and OAT10[141]	Preferential inhibition of urate reabsorption results in decreased SU
Losartan	Angiotensin II receptor antagonist (antihypertensive)	ABCG2 inhibitor[86]	Inhibitor of URAT1[134] and SLC2A9[133]
Fenofibrate	PPARα activator (cholesterol lowering)	Inhibitor of ABCG2[86, 142] and OAT3 [143]	Moderate inhibition of URAT1 [144]
Xanthine oxidase inhibitors (with net urinary urate excretion)
Allopurinol	Xanthine oxidase inhibitor	Substrate of ABCG2 [83, 84] and OAT2[145]	---	Decreased urate production with potential decreased urate secretion
Febuxostat	Xanthine oxidase inhibitor	ABCG2 inhibitor[86]	---
Topiroxostat†	Xanthine oxidase inhibitor	Inhibition of ABCG2[86], OAT1 and OAT3[81]	---

SU: serum urate; ---: No known interactions;

^†:clinical trials ongoing, drugs are not currently FDA approved in the US

^*Benzbromarone has been withdrawn in the US due to concerns with hepatotoxicity [146]