title: Effects of sodium bicarbonate and ammonium chloride pre-treatments on PEPT2 (SLC15A2) mediated renal clearance of cephalexin in healthy subjects.
abstract: PEPT2 mediates the H(+) gradient-driving reabsorption of di- and tri-peptides, and various peptidomimetic compounds in the kidney. This study examines the influence of urinary pH modification through sodium bicarbonate and ammonium chloride pre-treatments on the function of PEPT2 in healthy subjects, using cephalexin as the probe drug. Sixteen male subjects received a single oral dose of 1000 mg cephalexin under ammonium chloride and sodium bicarbonate treatment, respectively, with a wash-out period of one week. The study subjects were genotyped for PEPT2 polymorphic variants. Cephalexin concentrations in plasma and urine were determined by high performance liquid chromatography. The mean renal clearance of cephalexin was significantly higher under ammonium chloride treatment than that under sodium bicarbonate treatment (P < 0.01). This difference was significant for PEPT2*2/*2 (P = 0.017) but not for PEPT2*1/*1 (P = 0.128). No differences were observed for other pharmacokinetic parameters. The findings of this study suggest that urinary pH changes may alter the pharmacokinetics of PEPT2's substrates. This effect was more obvious for the PEPT2*2/*2.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Audrey May Yi
authors.initials: AM
authors.lastname: Tang
authors.forename: Yen Ling
authors.initials: YL
authors.lastname: Tan
authors.forename: Lie Michael George
authors.initials: LM
authors.lastname: Limenta
authors.forename: Edmund Jon Deoon
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D044466:Asian People; D002506:Cephalexin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D017693:Sodium Bicarbonate; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2; D000643:Ammonium Chloride; D017693:Sodium Bicarbonate; D002506:Cephalexin