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Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients

Märtson, A-G., van der Elst, K. C. M., Veringa, A., Zijlstra, J. G., Beishuizen, A., van der Werf, T. S., Kosterink, J. G. W., Neely, M. & Alffenaar, J-W., Sep-2020, In : Antimicrobial Agents and Chemotherapy. 64, 9, 10 p., ARTN e00905-20.

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The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions, measured on day 3 (+/- 1) of treatment. Pmetrics was used for population pharmacokinetic modeling and probability of target attainment (PTA). A target 24-h area under the concentration-time curve (AUC) value of 98 mg.h/liter was used as an efficacy parameter. Secondarily, the AUC/MIC targets of 450, 865, and 1,185 were used to calculate PTAs for Candida glabrata, C. albicans, and C. parapsilosis, respectively. The final 2-compartment model included weight as a covariate on volume of distribution (V). The mean V of the central compartment was 7.71 (standard deviation [SD], 2.70) liters/kg of body weight, the mean elimination constant (K-e) was 0.09 (SD, 0.04) h(-1), the rate constant for the caspofungin distribution from the central to the peripheral compartment was 0.44 (SD, 0.39) h(-1), and the rate constant for the caspofungin distribution from the peripheral to the central compartment was 0.46 (SD, 0.35) h(-1). A loading dose of 2 mg/kg on the first day, followed by 1.25 mg/kg as a maintenance dose, was chosen. With this dose, 98% of the patients were expected to reach the AUC target on the first day and 100% of the patients on the third day. The registered caspofungin dose might not be suitable for critically ill patients who were all overweight (>120 kg), over 80% of median weight (78 kg), and around 25% of lower weight (

Original languageEnglish
Article numberARTN e00905-20
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number9
Early online date13-Jul-2020
Publication statusPublished - Sep-2020

    Keywords

  • caspofungin, pharmacodynamics, pharmacokinetics, population pharmacokinetics, weight-based dosing, PHASE-II, MANAGEMENT, ANIDULAFUNGIN, CANDIDIASIS, GUIDELINE, ACCURATE, SOCIETY, PLASMA

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