Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters.
Article Details
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Li M, Anderson GD, Phillips BR, Kong W, Shen DD, Wang J
Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters.
Drug Metab Dispos. 2006 Apr;34(4):547-55. Epub 2006 Jan 24.
- PubMed ID
- 16434549 [ View in PubMed]
- Abstract
Amoxicillin and cefaclor are two of the widely used beta-lactam antibiotics in the treatment of urinary tract infections. Both drugs are eliminated mainly by the kidney and rely on renal excretion to exert their antibacterial activities in the urinary tract. Previous studies have suggested the involvement of organic anion and oligopeptide transporters in membrane transport of beta-lactams. The objective of the current study was to examine the kinetics of amoxicillin and cefaclor interactions with human renal transporters human organic anion transporter 1 (hOAT1), human peptide transporter 1 (hPepT1), and human peptide transporter 2 (hPepT2) in detail, both as substrates and as inhibitors. Using fluorescence protein tagging and cell sorting, we established Madin-Darby canine kidney cell lines stably expressing highly functional hOAT1, hPepT1, and hPepT2. Amoxicillin and cefaclor inhibited hOAT1-mediated [(3)H]para-aminohippuric acid uptake (K(i) = 11.0 and 1.15 mM, respectively). However, our uptake study revealed that neither drug was transported by hOAT1. Amoxicillin and cefaclor competitively inhibited hPepT2-mediated [(3)H]glycylsarcosine uptake (K(i) = 733 and 65 muM, respectively), whereas much lower affinity for hPepT1 was observed with both antibiotics. Direct uptake studies demonstrated that amoxicillin and cefaclor were transported by hPepT1 and hPepT2. Kinetic analysis showed that hPepT2-mediated uptake of both drugs was saturable with K(m) of 1.04 mM for amoxicillin and 70.2 muM for cefaclor. hPepT2, and to a lesser extent hPepT1, may play an important role in apical transport of amoxicillin and cefaclor in the renal tubule. hOAT1, in contrast, is not involved in basolateral uptake of these antibiotics.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Cefaclor Penicillin-binding protein 1A Protein Clostridium perfringens (strain 13 / Type A) YesInhibitorDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Aminohippuric acid Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Amoxicillin Solute carrier family 15 member 1 Protein Humans UnknownInhibitorDetails Amoxicillin Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails Amoxicillin Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Cefaclor Solute carrier family 15 member 1 Protein Humans UnknownInhibitorDetails Cefaclor Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails