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Updated: Sep 18, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
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.
Abstract:
Background: Amikacin is still an essential antimicrobial to treat life-threatening infections, including multidrug-resistant microorganisms. The effectiveness of treatment has been correlated with the Cmax/MIC ratio, with a ratio of 8 being recommended, which is difficult to reach in some patients. Appropriate antibiotic exposure is important for knowing the disposition of the drug in the population. Objectives: We aimed to integrate therapeutic drug monitoring and a populational pharmacokinetic model to assess an optimal dose regimen and respective plasma exposure. Methods: Plasma levels of amikacin in peaks and troughs were determined by LC-MS/MS. The pharmacokinetic parameter was estimated to use nonlinear mixed effect modeling in Monolix® software. The probability of target attainment was also determined using the Simulx™ software. Results: A total of 39 patients were enrolled. A one-compartment model with proportional error model best described amikacin pharmacokinetic parameters, providing a Cl of 1.49 L/h and Vc of 23.18 L. The model developed could characterize the pharmacokinetic profile in Brazilian patients who underwent therapeutic drug monitoring. Conclusions: Amikacin therapeutic drug monitoring should be associated with population pharmacokinetic analysis in dose optimization and individualization, helping maintain appropriate drug exposure in special populations such as critically ill patients. This strategy may contribute to enhancing clinical outcomes.
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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