Table 4.

Effect of Microbiota-Derived Uremic Toxins on Drug Transporters

Drug Transporter	Indoxyl Sulfate	p-Cresol OR p-Cresol Sulfate	Kynurenic Acid	CMPF	Hippuric Acid	Indole-3-Acetic Acid	Microbial Toxin Combination
OATP1B1	No effect on transport [69] * Inhibitor [68,85]#	Inhibitor [68] [71]#	Inhibitor [68]#	Inhibitor [69]* Decreased hepatic mRNA [67]* [85]#	No effect on transport [68,69]* [85]#	No effect on transport [69]* Inhibitor [68,85]# [71]*	Inhibit uptake (HA, IS, I3A, CMPF) [69]* (HA, IS, I3A, CMPF) [85] *
OATP1B3	No effect on transport [69]* Inhibitor [68,71]#	Inhibitor [68] [71]#	Inhibitor [68]#	Inhibitor [69]* [71]#	No effect on transport [69]* Inhibitor [68]#	No effect on transport [69]* Inhibitor [68]#	Inhibit uptake (HA, IS, I3A, CMPF) [69]*
OATP2	No effect on transport [56] *			Inhibitor [56]*	No effect on transport [56]*	No effect on transport [56]*
OATP2B1	No to minimal effect on intestinal or hepatic mRNA expression [67]* Inhibitor [71]#			No to minimal effect on intestinal mRNA expression [67]* Decreased hepatic mRNA [67]* Inhibitor [71]#	No to minimal effect on intestinal mRNA expression [67]* Decreased hepatic mRNA [67]*	No to minimal effect on intestinal or hepatic mRNA expression [67]*	Decrease in intestinal mRNA expression (HA, CMPF, I3A, IS) [67]*
OAT1	Inhibitor [73,79,80] [81]*	Inhibitor [74]*		Inhibitor [73]#, [81]*	Inhibitor [73] [81]*	Inhibitor [73]* [81]#
OAT3	Inhibitor [73,79-–81]*	Inhibitor [73]*		Inhibitor [73,81]*, [78]#	Inhibitor [73,81]*, [78]#	Inhibitor [73,78,81]#
MRP2	No to minimal effect on intestinal or hepatic mRNA expression [67]*			No to minimal effect on intestinal or hepatic mRNA expression [67]*	No to minimal effect on intestinal or hepatic mRNA expression [67]*	No to minimal effect on intestinal or hepatic mRNA expression [67]*	Decrease in intestinal mRNA expression (HA, CMPF, I3A, IS) [67]*
MRP4	Non-competitive inhibitor[82]*	No effect on transport [82]*	Inhibitor [82]*		Non-competitive inhibitor [82]*	Non-competitive inhibitor [82]*
BCRP	Non-competitive inhibitor [82]*	No effect on transport [82]*	Mixed inhibitor [82]*		Non-competitive inhibitor [82]*	No effect on transport [82]*

^*Denotes within clinically relevant concentrations,

^#Higher concentrations than observed in patients.

CMPF, 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid. HA, hippuric acid. IS, Indoxyl sulfate. I3A, Indole-3-acetic acid. PC, P-cresol.