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. 2023 Jun 1;14:3175. doi: 10.1038/s41467-023-38789-8

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© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — A Schematic diagram illustrating the mechanisms of action and metabolism of dFdC. B Schematic workflow illustrating Slc28a1^+/+ and Slc28a1^−/− mouse treatment and serial blood and urine collection after dFdC administration. Plasma pharmacokinetic profiling of C dFdC, D dFdU, and E dFdC-TP in Slc28a1^+/+ (black) and Slc28a1^−/− (red) mice receiving a single intravenous dose of dFdC (50 mg/kg). F Concentration-time data were analyzed by noncompartmental analysis, and pharmacokinetic parameters were calculated with WinNonlin (F, Table). Table shows plasma and urine pharmacokinetic parameters of dFdC and dFdU in Slc28a1^+/+ and Slc28a1^−/− mouse plasma. Abbreviations: C_max maximum plasma concentration, T_max, time at which the maximum plasma concentration is achieved, AUC area under the plasma concentration-time curve, T_1/2 the half-life of the terminal phase, CL systemic clearance, Vss volume of distribution at steady state, NS not significant. Urinary pharmacokinetic profiling of G dFdC, H dFdU, and I dFdC-TP in Slc28a1^+/+ (black) and Slc28a1^−/− (red) mice receiving a single intravenous dose of dFdC (50 mg/kg). Serial blood and urine sampling was performed at 5, 10, 15, 30, 60, 120, and 240 min, and analyte plasma and urine concentrations were determined by LC–MS/MS. Data represent the mean ± SEM (n = 6 mice/group). Plasma and urine pharmacokinetic profiling was performed in two independent experiments. *Footnote: (*p < 0.05 by two-tailed Welch’s t-test).