ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Impact of peptide transporter 1 on the intestinal absorption and pharmacokinetics of valacyclovir after oral dose escalation 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 24 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Phase Ib Trial To Evaluate the Safety and Pharmacokinetics of Multiple Ascending Doses of Filociclovir (MBX-400, Cyclopropavir) in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2019Trial
- Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.The Journal of membrane biology · 2025Review
- Valine-Niclosamide for Treatment of Androgen Receptor Splice Variant-Positive Hepatocellular Carcinoma.Cancers · 2025Article
- Design of an L-Valine-Modified Nanomicelle-Based Drug Delivery System for Overcoming Ocular Surface Barriers.Pharmaceutics · 2022Article
- Tissue-Specific Proteomics Analysis of Anti-COVID-19 Nucleoside and Nucleotide Prodrug-Activating Enzymes Provides Insights into the Optimization of Prodrug Design and Pharmacotherapy Strategy.ACS pharmacology & translational science · 2021Article
- Diabetes downregulates peptide transporter 1 in the rat jejunum: possible involvement of cholate-induced FXR activation.Acta pharmacologica Sinica · 2020Article
- The SLC transporter in nutrient and metabolic sensing, regulation, and drug development.Journal of molecular cell biology · 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
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Semi-Mechanistic Population Pharmacokinetic Modeling of L-Histidine Disposition and Brain Uptake in Wildtype and Pht1 Null Mice.Pharmaceutical research · 2018Article
- In Silico Absorption Analysis of Valacyclovir in Wildtype and Pept1 Knockout Mice Following Oral Dose Escalation.Pharmaceutical research · 2017Article
- Specific expression of proton-coupled oligopeptide transporter 1 in primary hepatocarcinoma-a novel strategy for tumor-targeted therapy.Oncology letters · 2017Article
- Potential Development of Tumor-Targeted Oral Anti-Cancer Prodrugs: Amino Acid and Dipeptide Monoester Prodrugs of Gemcitabine.Molecules (Basel, Switzerland) · 2017Article
- Arginyl dipeptides increase the frequency of NaCl-elicited responses via epithelial sodium channel alpha and delta subunits in cultured human fungiform taste papillae cells.Scientific reports · 2017Article
- Harnessing Solute Carrier Transporters for Precision Oncology.Molecules (Basel, Switzerland) · 2017Review
- 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
- 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
- Salt Bridge Swapping in the EXXERFXYY Motif of Proton-coupled Oligopeptide Transporters.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The primary objective of this study was to determine the in vivo absorption properties of valacyclovir, including the potential for saturable proton-coupled oligopeptide transporter 1 (PepT1)-mediated intestinal uptake, after escalating oral doses of prodrug within the clinical dose range. A secondary aim was to characterize the role of PepT1 on the tissue distribution of its active metabolite, acyclovir. [³H]Valacyclovir was administered to wild-type (WT) and PepT1 knockout (KO) mice by oral gavage at doses of 10, 25, 50, and 100 nmol/g. Serial blood samples were collected over 180 minutes, and tissue distribution studies were performed 20 minutes after a 25-nmol/g oral dose of valacyclovir. We found that the C(max) and area under the curve (AUC)₀₋₁₈₀ of acyclovir were 4- to 6-fold and 2- to 3-fold lower, respectively, in KO mice for all four oral doses of valacyclovir. The time to peak concentration of acyclovir was 3- to 10-fold longer in KO compared with WT mice. There was dose proportionality in the C(max) and AUC₀₋₁₈₀ of acyclovir in WT and KO mice over the valacyclovir oral dose range of 10-100 nmol/g (i.e., linear absorption kinetics). No differences were observed in the peripheral tissue distribution of acyclovir once these tissues were adjusted for differences in perfusing drug concentrations in the systemic circulation. In contrast, some differences were observed between genotypes in the concentrations of acyclovir in the distal intestine. Collectively, the findings demonstrate a critical role of intestinal PepT1 in improving the rate and extent of oral absorption for valacyclovir. Moreover, this study provides definitive evidence for the rational development of a PepT1-targeted prodrug strategy.
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Registered trials
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.