Population Pharmacokinetic Study of Prophylactic Fluconazole in Preterm Infants for Prevention of Invasive Candidiasis
- Authors
- Kim, Yu Kyong; Lee, Juyoung; Oh, Jaeseong; Rhee, Su-jin; Shin, Seung Han; Yoon, Seo Hyun; Lee, SeungHwan; Kim, Han-Suk; Yu, Kyung-Sang
- Issue Date
- Jun-2019
- Publisher
- American Society for Microbiology
- Keywords
- fluconazole; infant; premature; patient-specific modeling; pharmacokinetics
- Citation
- Antimicrobial Agents and Chemotherapy, v.63, no.6
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Antimicrobial Agents and Chemotherapy
- Volume
- 63
- Number
- 6
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/66054
- DOI
- 10.1128/AAC.01960-18
- ISSN
- 0066-4804
1098-6596
- Abstract
- Fluconazole is an antifungal agent with reported evidence for its prophylactic effect against systemic fungal infection in preterm infants. The aim of this study was to build a population pharmacokinetic model to evaluate the pharmacokinetic characteristics of intravenous and oral fluconazole in preterm infants with the current prophylactic fluconazole dosing regimen. A pharmacokinetic model was developed using 301 fluconazole concentrations from 75 preterm infants with a baseline body weight (WT) ranging from 0.5 to 1.5 kg and an estimated glomerular filtration rate (eGFR) ranging from 12.9 to 58.5 ml/min/1.73 m(2). Eligible infants received an intravenous or oral dose of 3 mg/kg of body weight of fluconazole, twice weekly with a >= 72-h dose interval, for 4 weeks. The model was qualified with basic goodness-of-fit diagnostics, visual predictive checks, and bootstrapping. The fluconazole pharmacokinetics was well described with a one-compartment linear model with a proportional residual error. The population clearance (CL) and volume of distribution (V) were derived as 0.0197 x (WT/1.00)(0.746) x (eGFR/25.0)(0.463) x exp(eta) and 1.04 x WT x exp(eta), respectively. Such covariate analyses augment the awareness of the need for personalized dosing in preterm infants.
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