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Antimicrob Agents Chemother. 1993 November; 37(11): 2327-2332

Stereoselective renal tubular secretion of carbenicillin.

Department of Pharmacokinetics and Biopharmaceutics, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

ABSTRACT

The stereoselective disposition of carbenicillin epimers was studied in healthy human volunteers. There was a difference between the two epimers in the extent of plasma protein binding in vitro, with the unbound fraction of the R epimer being greater than that of the S epimer. Renal clearance (CLR) of each epimer was greater than the glomerular filtration rate, suggesting renal tubular secretion of both epimers. Although the CLR was greater for the R epimer, renal tubular secretion was greater for the S epimer. When probenecid was coadministered, the CLR of each epimer was significantly reduced and was approximately equal to the glomerular filtration rate. The difference in CLR between the two epimers was simply due to differences in plasma protein binding. The observations in the present study suggest that both carbenicillin epimers are secreted by an organic anion transport system in the renal proximal tubule in humans and that the two epimers may be distinguished in the secretion process, resulting in the differences in the secretion rates.

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