Table 1b.

Drugs that Decrease Urinary Urate Excretion

Drug	Drug Action	Interactions with Urate Transporters (Secretion Pathway)	Interactions with Urate Transporters (Reabsorption Pathway)	Effects on Serum Urate
Loop Diuretics
Furosemide	NKCC2 Inhibitor (loop diuretic)	Inhibitor of ABCG2[86] and NPT4[58]; substrate of OAT3[85]	---	Direct inhibition of urate secretion with competitive inhibition of urate transport, leads to increased SU due to decreased secretion;
Bumetanide	NKCC2 Inhibitor (loop diuretic)	NPT4 inhibitor[58]; substrate of OAT1[85], OAT2[67], OAT3[85],	Substrate of OAT4[67]	Competitive inhibition of urate transport, leads to increased SU due to decreased secretion
Ethacrynic acid	NKCC2 Inhibitor (loop diuretic)	NPT4 inhibitor[58]; substrate of oAt3[85]	---
Torasemide	NKCC2 Inhibitor (loop diuretic)	Substrate of OAT1 and OAT3[147]	Substrate of OAT4[147]	Competitive inhibition of urate transport at the basolateral membrane, and increased urate uptake at the tubule lumen lead to increased SU
Thiazide Diuretics
Bendroflumethiazide	NCC inhibitor (diuretic)	Substrate of OAT1 and OAT3[148]	---	Competitive inhibition of urate transport, leads to increased SU due to decreased secretion Increased SU due to increased reabsorption
Chlorothiazide Cyclothiazide Trichlormethiazide	NCC Inhibitor (diuretic)	Substrate of OAT1[85]	---
Hydrochlorothiazide	NCC Inhibitor (diuretic)	Substrate of OAT1[85]	Substrate of OAT4[48]
SGLT2 Inhibitors
Canagliflozin	SLGT2 inhibitor (glucosuric)	Substrate of ABCG2, but not OAT1 or OAT3 [149]	URAT1 not inhibited but is required for uricosuric effect[74]	Uricosuric effects may be related to increased tubular glucose concentration[74, 87] or increased urate secretion, however the mechanisms are currently unknown
Dapagliflozin	SLGT2 inhibitor (glucosuric)	May improve OAT3 function[85]	Increased reduction in SU without influencing urate excretion in combination with febuxostat and verinurad [150]
Empagliflozin	SLGT2 inhibitor (glucosuric)	Substrate of ABCG2[81]; may upregulate ABCG2 expression [151]; some interactions with OAT3 and minimally with OAT1[152]	---
Ertugliflozin	SLGT2 inhibitor (glucosuric)	Substrate of ABCG2 [81]	---
Other Drugs
Aspirin	NSAID	Inhibition of OAT1 and OAT3 [153]	Substrate of URAT1[153]	Low does can increase SU due to increased reabsorption and decreased secretion High doses can cause inhibition of URAT1, with SU due to decreased reabsorption

SU: serum urate; NCC: Sodium Chloride Co-transporter; NKCC2: Sodium-Potassium-Chloride Co-transporter; PPARα: peroxisome proliferator-activated receptor alpha; SGLT2: sodium glucose cotransporter 2; NSAID: nonsteroidal anti-inflammatory drug; ---: No known interactions