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Updated: Jul 14, 2026
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
[Appropriate usage of antibiotics by therapeutic drug monitoring]
Hideya Kokubun1, Toshimi Kimura, Kazuo Yago
1Department of Pharmacy, Kitasato University Hospital, Japan. kokubun@kitasato-u.ac.jp
Insights
Neonates require higher aminoglycoside doses due to increased extracellular fluid volume and immature renal function. Arbekacin dosing for neonates should be based on post-conceptional age for optimal therapeutic drug monitoring.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Nephrology
Background:
- Aminoglycosides distribute widely in extracellular fluid, impacting dosing in neonates with higher fluid volumes.
- Neonatal renal function is immature, affecting drug excretion and requiring age-specific administration schedules.
- Therapeutic drug monitoring (TDM) is crucial for optimizing antibiotic efficacy and safety.
Purpose of the Study:
- To present TDM analysis results for antibiotics in a hospital setting.
- To establish optimized Arbekacin administration schedules for neonates based on post-conceptional age.
- To correlate vancomycin serum levels with patient parameters for dose adjustments in hemodialysis patients.
Main Methods:
- Analysis of Arbekacin volume of distribution (Vd) in neonates compared to adults.
- Evaluation of renal drug excretion in relation to post-conceptional age (PCA) in neonates.
- Correlation analysis between serum vancomycin levels, dose, serum creatinine (Scr), and weight in hemodialysis patients.
Main Results:
- Arbekacin Vd in neonates was twice that of adults (0.54 l/kg), necessitating higher weight-based doses.
- Renal drug excretion increased significantly in neonates at 34-35 weeks PCA, informing Arbekacin scheduling.
- A strong correlation was found between serum vancomycin levels and the ratio of dose x Scr/weight in hemodialysis patients.
Conclusions:
- Aminoglycoside dosing in neonates must account for increased Vd and immature renal function.
- Arbekacin administration schedules for neonates should be tailored to their post-conceptional age.
- Weight and serum creatinine are valuable parameters for guiding vancomycin and teicoplanin dosing in hemodialysis patients.
Abstract:
Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution is increased. In our data, the volume of distribution (Vd) of Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the dose per weight of aminoglycosides to the neonates should be increased more than to the adults. In the renal function of the neonates, differentiation of the nephron is completed within 36 weeks after conception, but it is functionally immature. In our data, renal drug excretion increased rapidly in the post-conceptional ages (PCAs) of 34-35 weeks. Consequently, we based the Arbekacin administration schedule for the neonates on the PCAs. There is excellent correlation between serum level of vancomicin (VCM) and dose x serum creatinine (Scr)/weight in the haemodialysis patients, suggesting that we can use weight and Scr to set the VCM administration schedule for these patients. We also established on administration schedule of Teicoplanin for the haemodialysis patients. In this article, we present the TDM analysis result of the antibiotics in our hospital.
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