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Related Concept Videos

Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

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In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
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Continuous Renal Replacement Therapy01:30

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Continuous Renal Replacement Therapy, also known as CRRT, is a procedural treatment for acute kidney injury (AKI) that gradually removes uremic toxins and fluids while maintaining acid-base balance and stabilizing electrolytes. It is particularly useful for hemodynamically unstable patients. Unlike intermittent hemodialysis, which is faster, CRRT provides a gentler approach over 24 hours, closely mimicking the function of natural kidneys. However, CRRT is not ideal for patients with...
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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
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Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy01:26

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Continuous Renal Replacement Therapy (CRRT) is an essential intervention for patients experiencing severe kidney dysfunction. This therapy offers a continuous mechanism for removing fluids and toxins from the bloodstream, leveraging the patient’s blood pressure to facilitate filtration through a specialized filter. This method contrasts with intermittent dialysis, providing a gentler and more consistent removal of waste products and excess fluid, which is particularly beneficial in...
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Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

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In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
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Drug Dosing: Infants and Children01:29

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Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
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Model-informed cefepime dosing in paediatric patients receiving continuous renal replacement therapy.

Ronaldo Morales Junior1, Shannon Reinert2, Emily Diseroad3

  • 1Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

International Journal of Antimicrobial Agents
|April 17, 2026
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Summary

Model-informed precision dosing (MIPD) optimized cefepime therapy for critically ill children on continuous renal replacement therapy (CRRT). This approach ensured effective antibiotic levels, avoiding toxicity and subtherapeutic exposures in pediatric CRRT patients.

Keywords:
Beta-lactamsExtracorporeal devicesPaediatricsPrecision dosingTherapeutic drug monitoring

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Area of Science:

  • Pediatric Critical Care Medicine
  • Pharmacokinetics and Pharmacodynamics
  • Renal Replacement Therapy

Background:

  • Critically ill children on CRRT face unpredictable cefepime exposure due to altered pharmacokinetics.
  • Subtherapeutic or toxic antibiotic levels can result from patient factors and CRRT parameters.
  • Optimizing cefepime dosing is crucial for effective treatment in this vulnerable population.

Purpose of the Study:

  • To describe the use of model-informed precision dosing (MIPD) for guiding cefepime therapy in pediatric patients undergoing CRRT.
  • To assess the feasibility and clinical utility of MIPD in achieving therapeutic cefepime concentrations.
  • To identify key factors influencing cefepime pharmacokinetics during CRRT.

Main Methods:

  • A case series of five critically ill pediatric patients receiving cefepime and CRRT.
  • Individual pharmacokinetic analyses using measured cefepime concentrations and a population PK model with a CRRT module.
  • Inclusion of CRRT prescription variables (effluent flow rate, blood flow, filter type) in the PK model.
  • Assessment of residual urine output and CRRT effluent flow rate as predictors of drug clearance.

Main Results:

  • CRRT contributed significantly to total cefepime clearance (26.9%–83.4%) across cases.
  • Residual urine output and CRRT effluent flow rate were identified as key predictors of cefepime clearance.
  • Extended cefepime infusions were required in three patients to reach target pharmacodynamic goals.
  • No patients required dose reduction due to concerns of excessive drug exposure.

Conclusions:

  • MIPD is a feasible and clinically useful strategy for optimizing cefepime dosing in pediatric CRRT.
  • Bedside pharmacokinetic consultation, incorporating patient-specific and CRRT factors, enhances cefepime therapy.
  • This approach helps achieve therapeutic targets and avoid adverse antibiotic exposures in critically ill children on CRRT.