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Pharmacokinetic modelling of caspofungin to develop an extended dosing regimen in paediatric patients
Silke Gastine1,2, Georg Hempel1, Michael N Neely3
1Institute of Pharmaceutical and Medical Chemistry, Deptartment of Clinical Pharmacy, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Background:
Echinocandins are commonly used in treatment and prophylaxis of invasive fungal diseases. Intravenous daily dosing for prophylaxis in the outpatient setting can however become a hurdle for adequate compliance in the paediatric population.
Objectives:
Simulations were performed to assess extended twice-weekly dosing for antifungal prophylaxis using caspofungin.
Methods:
A population pharmacokinetic model was developed based on previously published data from children aged 3 months to 17 years. Using the final model, Monte Carlo simulations were performed to assess the dose needed for adequate exposure in a twice-weekly setting. Mean weekly AUC0-24 h/MIC together with reported AUC0-24 h from previously reported paediatric trials were used to guide adequate exposure.
Results And Conclusions:
A two-compartment model with linear elimination and allometric scaling using fixed exponents was found most adequate to describe the given paediatric populations. Simulations showed that a 200 mg/m2 twice-weekly regimen with maximal 200 mg total dose should result in exposures matching registered daily dosing as well as commonly used pharmacokinetic/pharmacodynamic targets.
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