Interaction of human organic anion transporters with various cephalosporin antibiotics.

Article Details

Citation

Takeda M, Babu E, Narikawa S, Endou H

Interaction of human organic anion transporters with various cephalosporin antibiotics.

Eur J Pharmacol. 2002 Mar 8;438(3):137-42.

PubMed ID
11909604 [ View in PubMed
]
Abstract

Cephalosporin antibiotics are thought to be excreted into the urine via organic anion transporters (OATs). The purpose of this study was to elucidate the interaction of human-OATs with various cephalosporin antibiotics, using proximal tubule cells stably expressing human-OAT1, human-OAT3 and human-OAT4. Human-OAT1 and human-OAT3 are localized to the basolateral side of the proximal tubule, whereas human-OAT4 is localized to the apical side. The cephalosporin antibiotics tested were cephalothin, cefoperazone, cefazolin, ceftriaxone, cephaloridine, cefotaxime, cefadroxil and cefamandole. All of these cephalosporin antibiotics significantly inhibited organic anion uptake mediated by human-OAT1, human-OAT3 and human-OAT4. Kinetic analysis revealed that these inhibitions were competitive. The inhibition constant (K(i)) values of cefoperazone, cefazolin, ceftriaxone and cephaloridine for human-OAT1 were much lower than those for human-OAT3 and human-OAT4, whereas the K(i) values of cephalothin and cefotaxime for human-OAT3 were much lower than those for human-OAT1 and human-OAT4. Human-OAT4 mediated the bidirectional transport of estrone sulfate, an optimal substrate for human-OAT4. These results suggest that human-OAT1, human-OAT3 and human-OAT4 interact with various cephalosporin antibiotics, and that human-OAT1 and human-OAT3 play a distinct role in the basolateral uptake of cephalosporin antibiotics. Since the K(i) value of cephaloridine for human-OAT4-mediated organic uptake was much higher than that for human-OAT1, the results indicate the possibility that human-OAT4 limits the efflux of cephaloridine, leading to the accumulation of cephaloridine and the induction of nephrotoxicity.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CefotaximeSolute carrier family 22 member 11ProteinHumans
Unknown
Not AvailableDetails
CefotaximeSolute carrier family 22 member 6ProteinHumans
Unknown
Not AvailableDetails
CefotaximeSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
CeftriaxoneSolute carrier family 22 member 11ProteinHumans
Unknown
Not AvailableDetails
CeftriaxoneSolute carrier family 22 member 6ProteinHumans
Unknown
Not AvailableDetails
CeftriaxoneSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CefacetrileSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefacetrileSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefadroxilSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefadroxilSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefalotinSolute carrier family 22 member 11ProteinHumans
Unknown
Inhibitor
Details
CefalotinSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefalotinSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefamandoleSolute carrier family 22 member 11ProteinHumans
Unknown
Inhibitor
Details
CefamandoleSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefamandoleSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefazolinSolute carrier family 22 member 11ProteinHumans
Unknown
Inhibitor
Details
CefazolinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefazolinSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefoperazoneSolute carrier family 22 member 11ProteinHumans
Unknown
Inhibitor
Details
CefoperazoneSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefoperazoneSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CefotaximeSolute carrier family 22 member 11ProteinHumans
Unknown
Inhibitor
Details
CefotaximeSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefotaximeSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
CeftriaxoneSolute carrier family 22 member 11ProteinHumans
Unknown
Inhibitor
Details
CeftriaxoneSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CeftriaxoneSolute carrier family 22 member 8ProteinHumans
Unknown
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CefadroxilSolute carrier family 22 member 6Ki (nM)6140N/AN/ADetails
CefadroxilSolute carrier family 22 member 8Ki (nM)8620N/AN/ADetails
CefalotinSolute carrier family 22 member 11Ki (nM)200N/AN/ADetails
CefalotinSolute carrier family 22 member 6Ki (nM)220N/AN/ADetails
CefalotinSolute carrier family 22 member 8Ki (nM)40N/AN/ADetails
CefamandoleSolute carrier family 22 member 11Ki (nM)1140N/AN/ADetails
CefamandoleSolute carrier family 22 member 6Ki (nM)30N/AN/ADetails
CefamandoleSolute carrier family 22 member 8Ki (nM)46N/AN/ADetails
CefazolinSolute carrier family 22 member 11Ki (nM)1740N/AN/ADetails
CefazolinSolute carrier family 22 member 6Ki (nM)180N/AN/ADetails
CefazolinSolute carrier family 22 member 8Ki (nM)550N/AN/ADetails
CefoperazoneSolute carrier family 22 member 11Ki (nM)2800N/AN/ADetails
CefoperazoneSolute carrier family 22 member 6Ki (nM)210N/AN/ADetails
CefoperazoneSolute carrier family 22 member 8Ki (nM)1890N/AN/ADetails
CefotaximeSolute carrier family 22 member 11Ki (nM)6150N/AN/ADetails
CefotaximeSolute carrier family 22 member 6Ki (nM)3130N/AN/ADetails
CefotaximeSolute carrier family 22 member 8Ki (nM)290N/AN/ADetails
CeftriaxoneSolute carrier family 22 member 11Ki (nM)2380N/AN/ADetails
CeftriaxoneSolute carrier family 22 member 6Ki (nM)230N/AN/ADetails
CeftriaxoneSolute carrier family 22 member 8Ki (nM)4390N/AN/ADetails