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<p>Vadadustat is an innovative drug that inhibits prolyl hydroxylase and has been approved for the treatment of anemia in patients with chronic kidney disease. Its pharmacokinetics are linear, i.e., vadadustat’s absorption, distribution, and elimination are predictable. Vadadustat is well absorbed from the gastrointestinal tract, with over 99% of the drug bound to plasma proteins. The majority of the drug is conjugated with glucuronic acid in the liver, and these conjugates are primarily excreted through urine, with a smaller portion eliminated through stool. Only 1% of the unchanged drug is found in the urine, while 9% appears in the stool. In clinical trials, vadadustat demonstrated clear effectiveness compared with placebo, significantly increasing hemoglobin levels in patients with anemia due to chronic kidney disease, with an average increase of 1.43 ± 0.05 g/dL after 6 months of treatment. However, its effectiveness is somewhat lower than that of erythropoietin. The rates and severity of adverse events with vadadustat and erythropoietin are similar. Given that vadadustat is taken orally and has a beneficial efficacy and safety profile, it represents a meaningful addition to the standard treatment for anemia associated with renal failure, working alongside erythropoietin.</p>

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Clinical Pharmacokinetics and Pharmacodynamics of Vadadustat, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor

  • 期刊论文

  • 发表日期：

    2025年5月2日

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  • Slobodan M. Janković,
  • Snežana V. Janković

摘要

Vadadustat is an innovative drug that inhibits prolyl hydroxylase and has been approved for the treatment of anemia in patients with chronic kidney disease. Its pharmacokinetics are linear, i.e., vadadustat’s absorption, distribution, and elimination are predictable. Vadadustat is well absorbed from the gastrointestinal tract, with over 99% of the drug bound to plasma proteins. The majority of the drug is conjugated with glucuronic acid in the liver, and these conjugates are primarily excreted through urine, with a smaller portion eliminated through stool. Only 1% of the unchanged drug is found in the urine, while 9% appears in the stool. In clinical trials, vadadustat demonstrated clear effectiveness compared with placebo, significantly increasing hemoglobin levels in patients with anemia due to chronic kidney disease, with an average increase of 1.43 ± 0.05 g/dL after 6 months of treatment. However, its effectiveness is somewhat lower than that of erythropoietin. The rates and severity of adverse events with vadadustat and erythropoietin are similar. Given that vadadustat is taken orally and has a beneficial efficacy and safety profile, it represents a meaningful addition to the standard treatment for anemia associated with renal failure, working alongside erythropoietin.