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Background and Objective <p>Disulfiram (DSF) is a substance registered as an adjunct in the treatment of alcoholism, and its repurposing for several different diseases is under investigation. Our study aimed to investigate the pharmacokinetic behavior of DSF plasmatic metabolites (methyl diethyldithiocarbamate (Me-DDC) and S-methyl N,N-diethylthiocarbamate (Me-DTC) under fasting and fed conditions.</p> Methods <p>This is an exploratory phase 1, open label, randomized and crossover study where healthy participants took 250 mg or 500 mg of DSF tablets with or without a high-fat meal. Me-DDC and Me-DTC were extracted from blood plasma and quantified by mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis.</p> Results <p>Me-DDC and Me-DTC peak plasma concentrations (<i>C</i><sub>max</sub>) were higher when DSF was administered under fed condition. The exposure, estimated by the area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUC<sub>t</sub>), was approximately 100% higher for Me-DDC and 50% higher for Me-DTC when DSF (250 mg or 500 mg) was administered under fed condition. No significant differences were observed for both AUC<sub>t</sub> and AUC from time zero to infinity (AUC<sub>∞</sub>) normalized for the administered dose in those receiving 250 mg or 500 mg of DSF.</p> Conclusion <p>Administration of a high-fat meal before a single oral dose of DSF promoted a significant increase in the pharmacokinetic parameters <i>C</i><sub>max</sub>, AUC<sub>t</sub> and AUC<sub>∞</sub> for both metabolites. We also observed an apparent proportionality between the doses studied and pharmacokinetic parameters AUC<sub>t</sub> and AUC<sub>∞</sub> for both metabolites, indicating that metabolites may be good markers of exposure to DSF.</p>

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Randomized Study About Influence of Food on the Pharmacokinetics of Disulfiram Metabolites in Healthy Individuals

  • 期刊论文

  • 发表日期：

    2026年7月10日

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  • Gabriel P. E. Silveira,
  • Douglas P. Pinto,
  • Luciana F. Portela,
  • Sheila Suarez Fontes,
  • Juliana Almeida-Silva,
  • Alessandra L. Viçosa,
  • Sandra Aurora C. Perez,
  • Marcos André Vannier-Santos,
  • Rita Estrela,
  • Roberto M. Saraiva

摘要

Background and Objective

Disulfiram (DSF) is a substance registered as an adjunct in the treatment of alcoholism, and its repurposing for several different diseases is under investigation. Our study aimed to investigate the pharmacokinetic behavior of DSF plasmatic metabolites (methyl diethyldithiocarbamate (Me-DDC) and S-methyl N,N-diethylthiocarbamate (Me-DTC) under fasting and fed conditions.

Methods

This is an exploratory phase 1, open label, randomized and crossover study where healthy participants took 250 mg or 500 mg of DSF tablets with or without a high-fat meal. Me-DDC and Me-DTC were extracted from blood plasma and quantified by mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis.

Results

Me-DDC and Me-DTC peak plasma concentrations (Cmax) were higher when DSF was administered under fed condition. The exposure, estimated by the area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUCt), was approximately 100% higher for Me-DDC and 50% higher for Me-DTC when DSF (250 mg or 500 mg) was administered under fed condition. No significant differences were observed for both AUCt and AUC from time zero to infinity (AUC∞) normalized for the administered dose in those receiving 250 mg or 500 mg of DSF.

Conclusion

Administration of a high-fat meal before a single oral dose of DSF promoted a significant increase in the pharmacokinetic parameters Cmax, AUCt and AUC∞ for both metabolites. We also observed an apparent proportionality between the doses studied and pharmacokinetic parameters AUCt and AUC∞ for both metabolites, indicating that metabolites may be good markers of exposure to DSF.