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Pharmacokinetic evaluation of oral itraconazole for antifungal prophylaxis in children
Author(s) -
Allegra Sarah,
Fatiguso Giovanna,
De Francia Silvia,
Favata Fabio,
Pirro Elisa,
Carcieri Chiara,
De Nicolò Amedeo,
Cusato Jessica,
Di Perri Giovanni,
D'Avolio Antonio
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12822
Subject(s) - itraconazole , medicine , therapeutic drug monitoring , pharmacokinetics , dosing , confidence interval , logistic regression , pharmacology , antifungal , dermatology
Summary Itraconazole is a first‐generation triazole agent with an extended spectrum of activity; it is licensed in adults for superficial and systemic fungal infections; no recommendation has been yet established for use in children patients. Its variable and unpredictable oral bioavailability make it difficult to determine the optimal dosing regimen. Hence, therapeutic drug monitoring, highly available in clinical practice, may improve itraconazole treatment success and safety. The aim of the study was to describe in paediatrics the oral itraconazole pharmacokinetics, used for prophylaxis. Moreover, we evaluated the utility of its therapeutic drug monitoring in this cohort. A fully validated chromatographic method was used to quantify itraconazole concentration in plasma collected from paediatric patients, at the end of dosing interval. Associations between variables were tested using the Pearson test. Mann‐Whitney U test has been used to probe the influence of categorical variables on continuous ones. Any predictive power of the considered variables was finally evaluated through univariate and multivariate linear and logistic regression analyses. A high inter‐individual variability was shown; ethnicity (beta coefficient, β −0.161 and interval of confidence at 95%, IC −395.035; −62.383) and gender (β 0.123 and IC 9.590; 349.395) remained in the final linear regression model with P value of .007 and .038, respectively. This study highlights that therapeutic drug monitoring is required to achieve an adequate target itraconazole serum exposure.