Lack of renal secretion of carbenicillin in rats: poor affinity to the organic anion transporter at renal brush border membrane.
The renal secretion of carbenicillin (CBPC) was studied in rats. The results obtained in the in vivo study indicated very poor renal secretion of CBPC in rats, which was entirely different from those observed in humans and rabbits. In humans and rabbits, significant and stereoselective renal secretion of CBPC was observed in vivo. In order to verify the poor renal secretion of CBPC in rats, the transport characteristics of the organic anion transporters were studied in vitro using basolateral and brush border membrane vesicles. Transport of p-aminohippuric acid (PAH) into the basolateral membrane vesicles (BLMVs) was inhibited by CBPC, indicating that the organic anion transporter located at the BLM may have affinity to CBPC. In contrast, the transport of PAH into the brush border membrane vesicles (BBMVs) was not inhibited by CBPC, suggesting that the organic anion transporter located at the BBM may not have affinity to CBPC. Similar results were obtained for sulbenicillin (SBPC). Since CBPC and SBPC exist as di-anions at physiological pH, the organic anion transporter located at the rat renal BBM may not exhibit affinity to water-soluble di-anions, which in turn will result in poor renal secretion of these compounds.
Itoh
T
T
Department of Pharmacokinetics and Biopharmaceutics, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. itoht@pharm.kitasato-u.ac.jp
Koyano
S
S
Nakaura
H
H
Tsuda
Y
Y
Yamada
H
H
D000818:Animals; D027321:Anion Transport Proteins; D002228:Carbenicillin / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D010406:Penicillins / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D010406:Penicillins; D002228:Carbenicillin; D010130:p-Aminohippuric Acid