Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone.

Article Details

Citation

Uwai Y, Saito H, Inui K

Rat renal organic anion transporter rOAT1 mediates transport of urinary-excreted cephalosporins, but not of biliary-excreted cefoperazone.

Drug Metab Pharmacokinet. 2002;17(2):125-9.

PubMed ID
15618660 [ View in PubMed
]
Abstract

Most cephalosporin antibiotics are excreted into urine via glomerular filtration and active tubular secretion by renal organic anion transporters. In this study, we investigated the interaction of cephalosporins with rat organic anion transporter rOAT1, mainly expressed at the basolateral membrane of the renal proximal tubules, using Xenopus laevis oocytes, to assess the roles of rOAT1 in renal excretion of cephalosporin antibiotics. The expression of rOAT1 significantly stimulated the uptake of cefazolin, cefotiam and cephalexin into oocytes, but not of cefoperazone. The inhibition constants of these cephalosporins to rOAT1-mediated p-aminohippurate (PAH) uptake were 72 microM for cefazolin, 298 microM for cefoperazone, 718 microM for cefotiam and 6 mM for cephalexin. Eadie-Hofstee plot analysis revealed that cefoperazone as well as cefotiam inhibited rOAT1-mediated PAH uptake competitively. These results suggest that rOAT1 mediates basolateral uptake of cephalosporin antibiotics in the renal tubules. Furthermore, it is suggested that a minor contribution of the kidney to cefoperazone excretion could be related to the finding that cefoperazone is a poor substrate of rOAT1.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CefacetrileSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefacetrileSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefazolinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefoperazoneSolute carrier family 22 member 6ProteinHumans
Unknown
Inhibitor
Details
CefotiamSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CephalexinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details