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Related Concept Videos

Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

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Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
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Dialysis01:15

Dialysis

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Dialysis is a diffusion-based purification process that separates analyte molecules from a complex matrix. This is accomplished by allowing molecules in the solution to pass through a semipermeable membrane into a liquid on the other side. The membrane is usually made of cellulose acetate or cellulose nitrate, and the second liquid must be miscible with the solution. Ions (e.g., chloride or sodium) or organic molecules (e.g., glucose) can pass through the membrane pores, which generally have...
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Drug Elimination by Renal Route: Tubular Reabsorption01:22

Drug Elimination by Renal Route: Tubular Reabsorption

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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: Tubular Secretion01:28

Renal Drug Excretion: Tubular Secretion

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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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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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Enhanced Elimination of Poison01:26

Enhanced Elimination of Poison

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Poison can be effectively removed from the gastrointestinal (GI) tract through various decontamination procedures.
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
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Updated: Jun 6, 2025

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Target-controlled dialysis for antibiotics (TCD-ABx).

Alexander Dejaco1, Christoph Dorn2, Constantin Lier2

  • 1Department of Anaesthesiology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. alexander.dejaco@klinik.uni-regensburg.de.

Intensive Care Medicine Experimental
|November 26, 2024
PubMed
Summary

Target-controlled dialysis effectively adjusts antibiotic levels in critically ill patients undergoing renal replacement therapy. This novel method ensures therapeutic drug concentrations, preventing toxicity and resistance by optimizing antimicrobial therapy.

Keywords:
AntibioticsHemodialysisIntensive careRenal replacement therapyTarget-controlled dialysisTherapeutic drug monitoring

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Area of Science:

  • Pharmacology
  • Nephrology
  • Intensive Care Medicine

Background:

  • Renal replacement therapy significantly impacts antimicrobial pharmacokinetics in intensive care.
  • Managing antimicrobials with narrow therapeutic ranges during dialysis presents a challenge, balancing toxicity and efficacy.
  • Antimicrobial resistance is a growing concern linked to suboptimal drug exposure.

Purpose of the Study:

  • To investigate the feasibility of target-controlled dialysis for optimizing antimicrobial therapy.
  • To assess the ability of target-controlled dialysis to adjust drug concentrations towards therapeutic targets.
  • To evaluate the stability of key antibiotics in dialysis solutions.

Main Methods:

  • An in vitro continuous veno-venous hemodialysis model was used.
  • Five antibiotics (ceftazidime, meropenem, piperacillin/tazobactam, vancomycin, flucloxacillin) were tested.
  • Drug levels were quantified using high-performance liquid chromatography, and stability in dialysis solutions was assessed over 24 hours.

Main Results:

  • Target-controlled dialysis successfully shifted antibiotic concentrations towards target levels, irrespective of initial concentrations.
  • The method demonstrated effectiveness in both sub-therapeutic and supra-therapeutic initial drug level scenarios.
  • Antibiotic stability in dialysis solutions was confirmed, with minimal (<10.2%) loss over 12 hours.

Conclusions:

  • Target-controlled dialysis is mechanistically plausible and experimentally feasible for maintaining therapeutic antibiotic concentrations.
  • This technique offers a potential solution for optimizing antimicrobial therapy in critically ill patients on renal replacement therapy.
  • Further clinical trials are warranted to validate this approach in patient populations.