Pharmacokinetics of extended dose intervals of micafungin in haematology patients: Optimizing antifungal prophylaxis

E. W. Muilwijk, J. A. Maertens, W. J.F.M. van der Velden, R. Ter Heine, A. Colbers, D. M. Burger, D. Andes, K. Theunissen, N. M.A. Blijlevens, R. J.M. Brüggemann

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8 Citaten (Scopus)

Samenvatting

Background: Extended dosing intervals for micafungin could overcome the need for hospitalization for antifungal prophylaxis. Objectives: This multicentre, open-label, randomized trial compared the pharmacokinetics of 300 mg of micafungin given twice weekly with 100 mg once daily as antifungal prophylaxis in adult haematology patients at risk of developing invasive fungal disease. Secondary objectives were assessment of adequate exposure with an alternative dosing regimen of micafungin (700 mg once weekly) through Monte Carlo simulations and assessment of safety in this patient population. Patients and methods: Twenty adult patients were randomized to receive either 300 mg of micafungin twice weekly or 100 mg once daily for 8 days. Blood samples were drawn daily and pharmacokinetic curves were determined on days 4/5 and 8. Monte Carlo simulations were performed for both investigated regimens as well as a frequently proposed alternative regimen (700 mg once weekly). Results: The predicted median AUC0–168h (IQR) for a typical patient on the investigated regimens of 100 mg once daily and 300 mg twice weekly and the hypothetical regimen of 700 mg once weekly were 690 (583–829), 596 (485–717) and 704 (585–833) mgh/L, respectively. Conclusions: We observed comparable exposure with 300 mg of micafungin twice weekly and 100 mg of micafungin once daily. We provide the pharmacokinetic proof for an extended dosing regimen, which now needs to be tested in a clinical trial with hard endpoints.

Originele taal-2Engels
Pagina's (van-tot)3095-3101
Aantal pagina's7
TijdschriftJournal of Antimicrobial Chemotherapy
Volume73
Nummer van het tijdschrift11
DOI's
StatusGepubliceerd - 1 nov. 2018
Extern gepubliceerdJa

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