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Renal Drug Excretion: Tubular Reabsorption01:25

Renal Drug Excretion: Tubular Reabsorption

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Tubular reabsorption, a process occurring post-glomerular filtration of drugs in the renal tubule, is a critical determinant of drug half-life. During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. This...
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Renal Drug Excretion: Tubular Secretion01:28

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Active tubular secretion is a robust, energy-demanding process that utilizes carrier systems to transport drugs into renal tubules. The active renal secretion systems include the organic anion transporter (OAT) for weak acids and the organic cation transporter (OCT) for weak bases. Structurally similar drugs can compete for the same transporter, potentially leading to drug accumulation and toxicity. However, this principle can be exploited therapeutically. One example is probenecid (Probalan),...
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Drug Excretion: Miscellaneous Routes01:10

Drug Excretion: Miscellaneous Routes

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Drug excretion involves various organs, including the liver, intestines, skin, and eyes. In the case of drugs or toxins, they can be actively secreted into bile by transporters in the hepatocyte's canalicular membrane. These substances enter the GI tract during digestion and may be reabsorbed into the body from the intestine. This process, known as enterohepatic recycling, can significantly prolong the presence and effects of a substance in the body. To interrupt this cycle, specific...
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One-Compartment Open Model: Urinary Excretion Data and Determination of k01:11

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The one-compartment open model leverages urinary excretion data to estimate renal clearance, which gauges the kidney's capacity to expel a drug. This method offers several benefits, including directly measuring drug elimination and assessing the kidney's contribution to overall drug clearance. However, this approach has limitations. It assumes sole renal excretion of the drug, which is not true for all drugs. Accurate urinary excretion and plasma drug concentration measurement can also...
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Drug Elimination by Renal Route: Tubular Reabsorption01:22

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During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
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Renal Drug Excretion: Overview01:15

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As primary excretory organs, the kidneys maintain homeostasis by removing waste substances from the bloodstream. They comprise over a million units called nephrons, which serve as the kidney's functional units.
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Long-Term Excretion of Roxadustat in Urine.

Tim Sobolevsky1, Matthew Fedoruk2, Frank Dellanna3

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Roxadustat, a drug for anemia, is detectable in urine for up to 18 months after treatment stops. This prolonged excretion pattern is crucial for doping control in sports.

Keywords:
FG‐4592dopinglong‐term excretionpharmacokineticsroxadustat

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Area of Science:

  • Pharmacology and Sports Science
  • Analytical Chemistry

Background:

  • Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase stabilizer used to treat anemia in chronic kidney disease patients.
  • Its erythropoiesis-enhancing properties lead to its prohibition in sports due to performance-enhancing potential.
  • Adverse analytical findings in doping controls have been reported, with some linked to contaminated supplements.

Purpose of the Study:

  • To investigate the long-term excretion pattern of roxadustat in urine.
  • To provide data relevant to anti-doping agencies for results management.

Main Methods:

  • Analysis of roxadustat excretion in urine after single-dose administration.
  • Monitoring roxadustat levels in anemic patients undergoing treatment.
  • Tracking roxadustat detection in an athlete with a history of use.

Main Results:

  • Roxadustat remained detectable in urine for up to 8 months after a single dose (<10 pg/mL).
  • In patients treated thrice weekly, urine samples showed detectable roxadustat between 9 and 18 months post-discontinuation.
  • An athlete tested positive for roxadustat 12 months after cessation of use, with continued detection for 15 months.

Conclusions:

  • Roxadustat exhibits unusually prolonged terminal excretion kinetics.
  • The extended detection window necessitates consideration by anti-doping authorities in their testing and results management protocols.