Stereoselective disposition of sulbenicillin in humans.

Antimicrobial Agents and Chemotherapy
T ItohH Yamada

Abstract

Stereoselective disposition of sulbenicillin (SBPC) epimers in healthy human volunteers was studied in order to clarify the differences in pharmacokinetic behavior between the epimers. Stereospecific high-performance liquid chromatography was used for the determination of SBPC epimers. Plasma protein binding was measured in vitro with an ultrafiltration method. The binding was stereoselective, with the unbound fraction (fu) of the R-epimer being approximately 1.3-fold greater than that of the S-epimer. SBPC was administered intravenously to human volunteers, and concentrations of SBPC in plasma and urinary excretion rates were measured. Renal clearance (CLR) for the unbound drug (approximately 400 ml/min) was greater than the glomerular filtration rate (GFR) (approximately 109 ml/min) for both epimers, suggesting that both epimers are secreted at the renal tubules. Renal tubular secretion appeared to be greater for the S-epimer. When probenecid was coadministered, the CLR values of both epimers were significantly reduced and were approximately equal to the GFR values. CLR was greater for the S-epimer (37.5 and 49.8 ml/min for R-SBPC and S-SBPC, respectively), which was simply due to the greater fu of the S-epimer in plasma. In ...Continue Reading

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Citations

Feb 23, 2021·ACS Pharmacology & Translational Science·Mayra Quemé-PeñaTamás Beke-Somfai
Feb 18, 2017·Clinical Pharmacokinetics·Anton IvanyukThierry Buclin
Jul 25, 2006·Expert Opinion on Drug Metabolism & Toxicology·Meng LiJoanne Wang

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