{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:08:51Z","timestamp":1760058531064,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Doctoral School of Poznan University of Medical Sciences in Poznan, Poland","award":["SDUM-DGB 01\/04\/2023"],"award-info":[{"award-number":["SDUM-DGB 01\/04\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: A population pharmacokinetic (popPK) model was used to evaluate fluconazole dosing regimens for Candida spp. prophylaxis in hemato-oncologic pediatric patients. Methods: Data were collected from patients receiving 3\u201312 mg\/kg of fluconazole once daily as a 0.5 or 1 h infusion. Fluconazole concentrations were determined using a validated HPLC-UV method. The popPK model employed non-linear mixed effects modeling using the FOCEI algorithm implemented in nlmixr2. Monte Carlo simulations and probability of target attainment (PTA) analysis were performed in the rxode2 package to investigate dosing recommendations. Results: Concentration time data from nine patients, aged 7 months to 18 years, with 35 samples, were described by a one-compartment model with first-order elimination and allometric scaling of body weight. Assuming a Candida spp. MIC = 2 mg\/L and the ratio of the area under the unbound concentration\u2013time curve at a steady state to the MIC (fAUC\/MIC) \u2265 100 as the pharmacokinetic\/pharmacodynamic (PK\/PD) target, the standard dosing regimens reported in the Summary of Product Characteristics (SmPC) did not achieve the target for patients treated with doses &lt; 6 mg\/kg. Conclusions: Hemato-oncologic pediatric patients require increased fluconazole doses to attain therapeutic efficacy. These results warrant clinical validation and should be confirmed by assessing a larger number of patients.<\/jats:p>","DOI":"10.3390\/pharmaceutics17040488","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T05:59:00Z","timestamp":1744091940000},"page":"488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluconazole Dosing for the Prevention of Candida spp. Infections in Hemato-Oncologic Pediatric Patients: Population Pharmacokinetic Modeling and Probability of Target Attainment Simulations"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-9975","authenticated-orcid":false,"given":"Arkadiusz","family":"Adamiszak","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7239-4035","authenticated-orcid":false,"given":"Katarzyna","family":"Derwich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-2346","authenticated-orcid":false,"given":"Alicja","family":"Bartkowska-\u015aniatkowska","sequence":"additional","affiliation":[{"name":"Department of Paediatric Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Pietrzkiewicz","sequence":"additional","affiliation":[{"name":"Department of Paediatric Anaesthesiology and Intensive Therapy, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabela","family":"Niewiadomska-Wojna\u0142owicz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-8326","authenticated-orcid":false,"given":"Andrzej","family":"Czyrski","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4027-0550","authenticated-orcid":false,"given":"William J.","family":"Jusko","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7272-5738","authenticated-orcid":false,"given":"Agnieszka","family":"Bienert","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Janowski, M., Demchuk, O.M., and Wujec, M. 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