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Prediction of Unbound Ceftriaxone Concentration in Children: Simple Bioanalysis Method and Basic Mathematical
Min Kan1, Hai-Yan Shi2, Bing Han3
1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Antimicrobial Agents and Chemotherapy
|October 6, 2020
Summary
Predicting unbound ceftriaxone concentrations in children is crucial for effective treatment. A validated disease-adapted equation offers a reliable method to estimate these levels, improving clinical practice.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Pediatric Pharmacology
- Analytical Chemistry
Background:
- Ceftriaxone's pharmacological activity is linked to its unbound concentration.
- Direct measurement of unbound ceftriaxone is challenging, with significant inter-individual variability observed in children.
- Accurate prediction of unbound drug levels is essential for optimizing pediatric therapy.
Purpose of the Study:
- To evaluate and validate a predictive method for unbound ceftriaxone concentrations in pediatric patients.
- To compare the performance of different predictive equations.
Main Methods:
- Developed and validated a bioanalysis method for measuring total and unbound ceftriaxone concentrations.
- Assessed predictive performance using mean absolute prediction error (MAPE), mean prediction error (MPE), P30, P50, and R².
- Analyzed 95 concentration pairs from 92 pediatric patients.
Main Results:
- The unbound fraction of ceftriaxone exhibited substantial variability (4.75%–39.97%).
- The disease-adapted equation demonstrated superior predictive performance compared to empirical in vivo and multiple linear regression equations.
- Key performance metrics for the disease-adapted equation included MPE of 0.00, MAPE of 0.15, P30 of 89.5%, P50 of 97.9%, and R² of 0.9342.
Conclusions:
- A validated bioanalysis method for total ceftriaxone and a predictive equation for unbound concentrations have been developed.
- The disease-adapted equation is recommended for clinical practice and research involving unbound ceftriaxone in children.
- The proposed method facilitates improved therapeutic drug monitoring and research in pediatric populations.
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