ArticleBiochemical pharmacology2016
Species differences in the pharmacokinetics of cefadroxil as determined in wildtype and humanized PepT1 mice.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Organoids and tissue/organ chips.Stem cell research & therapy · 2024Article
- In Vitro In Vivo Extrapolation and Bioequivalence Prediction for Immediate-Release Capsules of Cefadroxil Based on a Physiologically-Based Pharmacokinetic ACAT Model.AAPS PharmSciTech · 2024Article
- Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research.Stem cell research & therapy · 2024Article
- Tubeimoside-1: A review of its antitumor effects, pharmacokinetics, toxicity, and targeting preparations.Frontiers in pharmacology · 2022Review
- 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
- Establishment of SLC15A1/PEPT1-Knockout Human-Induced Pluripotent Stem Cell Line for Intestinal Drug Absorption Studies.Molecular therapy. Methods & clinical development · 2020Article
- Mechanisms of gemcitabine oral absorption as determined by in situ intestinal perfusions in mice.Biochemical pharmacology · 2019Article
- In Silico Prediction of the Absorption and Disposition of Cefadroxil in Humans using an Intestinal Permeability Method Scaled from HumanizedDrug metabolism and disposition: the biological fate of chemicals · 2019Article
- Effect of biphenyl hydrolase-like (BPHL) gene disruption on the intestinal stability, permeability and absorption of valacyclovir in wildtype and Bphl knockout mice.Biochemical pharmacology · 2018Article
- Evaluating the intestinal and oral absorption of the prodrug valacyclovir in wildtype and huPepT1 transgenic mice.Biochemical pharmacology · 2018Article
- Expression and regulation of proton-coupled oligopeptide transporters in colonic tissue and immune cells of mice.Biochemical pharmacology · 2018Article
- Pharmacokinetics and Bioavailability Study of Tubeimoside I in ICR Mice by UPLC-MS/MS.Journal of analytical methods in chemistry · 2018Article
- In Silico Absorption Analysis of Valacyclovir in Wildtype and Pept1 Knockout Mice Following Oral Dose Escalation.Pharmaceutical research · 2017Article
- Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
PepT1 (SLC15A1) is a high-capacity low-affinity transporter that is important in the absorption of digested di/tripeptides from dietary protein in the small intestine. PepT1 is also crucial for the intestinal uptake and absorption of therapeutic agents such as the β-lactam aminocephalosporins and antiviral prodrugs. Species differences, however, have been observed in PepT1-mediated intestinal absorption and pharmacokinetics, thereby, making it more difficult to predict systemic drug exposure. In the present study, we evaluated the in situ intestinal permeability of the PepT1 substrate cefadroxil in wildtype and humanized PepT1 (huPepT1) mice, and the in vivo absorption and disposition of drug after escalating oral doses. The in situ perfusions indicated that cefadroxil had a twofold higher affinity (i.e., twofold lower Km) for jejunal PepT1 in huPepT1 mice, lower but substantial permeability in all regions of the small intestine, and low but measureable permeability in the colon as compared to wildtype animals. The in vivo experiments indicated almost superimposable pharmacokinetic profiles between the two genotypes after intravenous bolus dosing of cefadroxil. In contrast, after oral dose escalation, the systemic exposure of cefadroxil was reduced in huPepT1 mice as compared to wildtype animals. Moreover, the AUC and Cmax versus dose relationships were nonlinear for huPepT1 but not wildtype mice, and similar to that observed from human subjects. In conclusion, our findings indicate that huPepT1 mice may provide a valuable tool in the drug discovery process by better predicting the oral pharmacokinetic profiles of PepT1 substrates in humans.
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