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- W2971497504 abstract "ABSTRACT The pharmacokinetic characterization of a drug, especially the determination of its biological half-life, is an essential step during the early phases of drug development. An adequate half-life is amongst the many properties needed for selecting a drug candidate for clinical trials. Conversely, drug candidates possessing inadequate half-lives may be modified or eliminated from the drug discovery pipeline altogether. Several methods exist for determining the half-lives of drugs, namely HPLC, fluorescence assays, radioassays, radioimmunoassays, and elemental mass spectrometric assays. However, all these techniques are resource and labor-intensive, and cannot be used for the high-throughput half-life determination of hundreds of drug candidates. Here, we describe TOX HL : a simple technique to determine the half-lives of compounds displaying noncumulative toxicity. To calculate the half life, TOX HL only relies on the survival outcomes of three experiments performed on an animal model: an acute toxicity experiment, a cumulative toxicity experiment, and a multi-dose experiment at different dosing intervals. As a proof of concept, we use TOX HL to determine the peritoneal half-life of Ω76, an antimicrobial peptide. The half-life of Ω76 determined by TOX HL is in good agreement with results from a standard mass spectrometric method, validating this approach." @default.
- W2971497504 created "2019-09-12" @default.
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- W2971497504 date "2019-09-08" @default.
- W2971497504 modified "2023-10-05" @default.
- W2971497504 title "A simple method to determine the elimination half-life of drugs displaying noncumulative toxicity" @default.
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- W2971497504 doi "https://doi.org/10.1101/761585" @default.
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