ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Significance of peptide transporter 1 in the intestinal permeability of valacyclovir in wild-type and PepT1 knockout mice.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Computational theranostics strategy for pancreatic ductal adenocarcinoma.Molecular diversity · 2026Article
- The Role of Metabolites in Acyclovir-Induced Neurotoxicity and Nephrotoxicity.Medicines (Basel, Switzerland) · 2026Review
- Stereoselective design of amino acid bioconjugates: targeting strategies and physicochemical optimization.RSC medicinal chemistry · 2026Review
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- The Application of Prodrugs as a Tool to Enhance the Properties of Nucleoside Reverse Transcriptase Inhibitors.Viruses · 2023Review
- Gutsy science: In vitro systems of the human intestine to model oral drug disposition.Pharmacology & therapeutics · 2022Review
- Evaluation of Excipient Risk in BCS Class I and III Biowaivers.The AAPS journal · 2022Review
- Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.Science advances · 2021Article
- Rapid and Sensitive Quantification of Intracellular Glycyl-Sarcosine for Semi-High-Throughput Screening for Inhibitors of PEPT-1.Pharmaceutics · 2021Article
- Diabetes downregulates peptide transporter 1 in the rat jejunum: possible involvement of cholate-induced FXR activation.Acta pharmacologica Sinica · 2020Article
- Recent advances in understanding prodrug transport through the SLC15 family of proton-coupled transporters.Biochemical Society transactions · 2020Review
- Structural basis for prodrug recognition by the SLC15 family of proton-coupled peptide transporters.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Absorption, Distribution, Metabolism, and Excretion of the Novel Helicase-Primase Inhibitor, Amenamevir (ASP2151), in Rodents.European journal of drug metabolism and pharmacokinetics · 2018Article
- Evaluating the intestinal and oral absorption of the prodrug valacyclovir in wildtype and huPepT1 transgenic mice.Biochemical pharmacology · 2018Article
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- In Silico Absorption Analysis of Valacyclovir in Wildtype and Pept1 Knockout Mice Following Oral Dose Escalation.Pharmaceutical research · 2017Article
- Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years.Molecules (Basel, Switzerland) · 2017Review
- Potential Development of Tumor-Targeted Oral Anti-Cancer Prodrugs: Amino Acid and Dipeptide Monoester Prodrugs of Gemcitabine.Molecules (Basel, Switzerland) · 2017Article
- 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
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The purpose of this study was to quantitatively determine the contribution of PepT1 [peptide transporter 1 (SLC15A1)] to the intestinal permeability of valacyclovir, an ester prodrug of the antiviral drug acyclovir. In situ single-pass intestinal perfusions were employed (pH 6.5 × 90 minutes) to assess the effective permeability (P(eff)) of 100 μM [(3)H]valacyclovir in wild-type and PepT1 knockout mice. Acyclovir pharmacokinetics was also evaluated after oral administration of 25 nmol/g valacyclovir. In wild-type mice, jejunal uptake of valacyclovir was best described by both saturable (K(m) = 10.2 mM) and nonsaturable components where the saturable pathway accounted for 82% of total transport. Valacyclovir P(eff) was 2.4 × 10(-4) cm/s in duodenum, 1.7 × 10(-4) cm/s in jejunum, 2.1 × 10(-4) cm/s in ileum, and 0.27 × 10(-4) cm/s in colon. In Pept1 knockout mice, P(eff) values were about 10% of that in wild-type animals for these small intestinal segments. Valacyclovir P(eff) was similar in the colon of both genotypes. There were no differences in valacyclovir P(eff) between any of the intestinal segments of PepT1 knockout mice. Valacyclovir P(eff) was significantly reduced by the dipeptide glycylsarcosine and the aminocephalosporin cefadroxil, but not by the amino acids l-valine or l-histidine, the organic acid p-aminohippurate, or the organic base tetraethylammonium (all at 25 mM). PepT1 ablation resulted in 3- to 5-fold reductions in the in vivo rate and extent of valacyclovir absorption. Our findings conclusively demonstrate, using in situ and in vivo validations in genetically modified mice, that PepT1 has a major influence in improving the oral absorption of valacyclovir.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.