ArticlePharmaceutical research2013
In vivo absorption and disposition of cefadroxil after escalating oral doses in wild-type and PepT1 knockout mice.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Physiologically Based Pharmacokinetic Modeling of Cefadroxil in Mouse, Rat, and Human to Predict Concentration-Time Profile at Infected Tissue.Frontiers in pharmacology · 2021Article
- Diabetes downregulates peptide transporter 1 in the rat jejunum: possible involvement of cholate-induced FXR activation.Acta pharmacologica Sinica · 2020Article
- Using Ex Vivo Porcine Jejunum to Identify Membrane Transporter Substrates: A Screening Tool for Early-Stage Drug Development.Biomedicines · 2020Article
- Evaluating the intestinal and oral absorption of the prodrug valacyclovir in wildtype and huPepT1 transgenic mice.Biochemical pharmacology · 2018Article
- Impact of P-Glycoprotein on Intestinal Absorption of an Inhibitor of Apoptosis Protein Antagonist in Rats: Mechanisms of Nonlinear Pharmacokinetics and Food Effects.Pharmaceutical research · 2018Article
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Tenapanor administration and the activity of the HBritish journal of clinical pharmacology · 2017Article
- Role of cephalosporins in the era of Clostridium difficile infection.The Journal of antimicrobial chemotherapy · 2017Review
- Species differences in the pharmacokinetics of cefadroxil as determined in wildtype and humanized PepT1 mice.Biochemical pharmacology · 2016Article
- The proton-coupled oligopeptide transporter 1 plays a major role in the intestinal permeability and absorption of 5-aminolevulinic acid.British journal of pharmacology · 2016Article
- Population pharmacokinetic modeling of cefadroxil renal transport in wild-type and Pept2 knockout mice.Xenobiotica; the fate of foreign compounds in biological systems · 2016Article
- Development and characterization of a novel mouse line humanized for the intestinal peptide transporter PEPT1.Molecular pharmaceutics · 2014Article
- Impact of peptide transporter 1 on the intestinal absorption and pharmacokinetics of valacyclovir after oral dose escalation in wild-type and PepT1 knockout mice.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Proton-coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications.Molecular aspects of medicineReview
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2 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug.
methodsThe absorption and disposition kinetics of [3H]cefadroxil were determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil were also determined in both genotypes after 44.5 nmol/g intravenous bolus doses.
resultsPepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil were not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations.
conclusionsThe findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs.
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