Therapeutic Drug Monitoring-Based Population Pharmacokinetics of Amikacin in Patients at a Teaching Hospital

Nadine Arnold Steffens1, Estevan Sonego Zimmermann2, Francine Johansson Azeredo2

  • 1Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Av. Roraima, 1000, Camobi, Santa Maria 97105-900, RS, Brazil.

Insights

Optimizing amikacin dosing through therapeutic drug monitoring and pharmacokinetic modeling helps achieve effective drug exposure. This approach is crucial for treating serious infections, especially in critically ill patients, improving treatment outcomes.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Clinical Pharmacy

Background:

  • Amikacin is vital for treating severe infections, including those caused by multidrug-resistant organisms.
  • Treatment success correlates with the Cmax/MIC ratio, but achieving the recommended ratio of 8 is challenging in some patients.
  • Understanding amikacin disposition through appropriate antibiotic exposure is critical.

Purpose of the Study:

  • To integrate therapeutic drug monitoring with a population pharmacokinetic model.
  • To assess optimal amikacin dosage regimens and associated plasma exposure.
  • To improve amikacin treatment efficacy in diverse patient populations.

Main Methods:

  • Plasma amikacin levels (peaks and troughs) were measured using LC-MS/MS.
  • Nonlinear mixed-effects modeling (Monolix®) estimated pharmacokinetic parameters.
  • Probability of target attainment was evaluated using Simulx™ software.

Main Results:

  • A one-compartment model with proportional error best described amikacin pharmacokinetics.
  • Key pharmacokinetic parameters identified: Cl of 1.49 L/h and Vc of 23.18 L.
  • The developed model accurately characterized amikacin pharmacokinetics in Brazilian patients undergoing TDM.

Conclusions:

  • Combining amikacin therapeutic drug monitoring with population pharmacokinetic analysis is recommended for dose optimization.
  • This integrated strategy aids in individualizing amikacin therapy and ensuring adequate drug exposure.
  • The approach supports improved clinical outcomes, particularly in special populations like critically ill patients.

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