ArticleJournal of pharmaceutical sciences2016
Interspecies Differences in the Metabolism of a Multiester Prodrug by Carboxylesterases.
Article in Journal of pharmaceutical sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 22 citations in OpenAlex.
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- A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market.Molecules (Basel, Switzerland) · 2021Article
- Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines.Journal of pharmaceutical analysis · 2020Article
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- Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion.Science (New York, N.Y.) · 2019Article
- Enhanced Oral Bioavailability of 2-(Phosphonomethyl)-pentanedioic Acid (2-PMPA) from its (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl (ODOL)-Based Prodrugs.Molecular pharmaceutics · 2019Article
- Tumor-Targeted Delivery of 6-Diazo-5-oxo-l-norleucine (DON) Using Substituted Acetylated Lysine Prodrugs.Journal of medicinal chemistry · 2019Article
- N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders.Journal of medicinal chemistry · 2017Article
- Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug.The AAPS journal · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The pentaethyl ester prodrug of the chelating agent diethylene triamine pentaacetic acid (DTPA) referred to as C2E5 is being developed as an orally bioavailable radionuclide decorporation agent. The predicted human efficacy obtained in these experimental animals is confounded by interspecies variations of metabolism. Therefore, in the present study, carboxylesterase-mediated metabolism of [(14)C]-C2E5 was compared in the S9 intestinal and hepatic fractions of human, dog, and rat and their respective plasma. Intestinal hydrolysis of C2E5, resulting in the formation of the tetraethyl ester of DTPA (C2E4), was only detected in human and rat. The primary metabolite in human and dog hepatic fractions was C2E4, whereas the predominant species identified in rat hepatic fractions was the triethyl ester (C2E3). Hepatic hydrolysis of C2E5 causes the formation of C2E4 in human, dog, and rat and C2E3 in rat only. Minimal C2E5 hydrolysis was observed in human and dog plasma, whereas in rat plasma C2E5 converted to C2E3 rapidly, followed by slower further metabolism. Both recombinant CES1 and CES2 play roles in C2E5 metabolism. Together, these data suggest that dogs may be the most appropriate species for predicting human C2E5 metabolism, whereas rats might be useful for clarifying the potential toxicity of C2E5 metabolites.
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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.