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Factors Associated With Voriconazole Concentration in Pediatric Patients
Suyeon Kang1,2, Jeong Yee3, Jae Youn Kim2
1Graduate School of Converging Clinical & Public Health, Ewha Womans University.
Insights
Predicting voriconazole levels in children is challenging. Oral administration and C-reactive protein levels are linked to low concentrations, while alanine aminotransferase indicates high levels, guiding therapeutic drug monitoring.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Clinical Chemistry
Background:
- Voriconazole pharmacokinetics are complex, making serum concentration prediction difficult in pediatric patients.
- Variability in voriconazole levels necessitates identification of influencing factors for optimized dosing.
Purpose of the Study:
- To identify factors associated with voriconazole trough concentrations in pediatric patients.
- To understand predictors of sub-therapeutic and supra-therapeutic voriconazole levels.
Main Methods:
- Retrospective cohort study of pediatric patients (<18 years) treated with voriconazole (Jan 2010 - Aug 2017).
- Analysis of electronic medical records for demographic data, treatment regimens, and potential influencing factors.
- Defined therapeutic range as 1.0-5.5 mcg/mL; concentrations outside this range were the study outcome.
Main Results:
- Oral administration and elevated C-reactive protein (CRP) levels were independently associated with low voriconazole trough concentrations (<1.0 mcg/mL).
- Higher alanine aminotransferase levels significantly predicted high voriconazole trough concentrations (>5.5 mcg/mL), even after adjusting for covariates (OR 5.42).
Conclusions:
- Monitoring specific parameters like CRP and liver enzymes is crucial for optimizing voriconazole therapy in children.
- Considering the route of administration (oral vs. IV) can aid in achieving therapeutic voriconazole concentrations and preventing adverse effects.
Background:
Serum concentrations of voriconazole are difficult to predict, especially in pediatric patients, because of its complex pharmacokinetic characteristics. This study aimed to identify the factors associated with the concentration of voriconazole in pediatric patients.
Methods:
This cohort study was based on retrospective data collection and involved the administration of voriconazole to pediatric patients younger than 18 years, between January 2010 and August 2017. Electronic medical records of the patients were reviewed to collect demographic characteristics, voriconazole treatment regimen, and factors that could potentially influence voriconazole trough concentrations. A voriconazole trough serum concentration of less than 1.0 mcg/mL or greater than 5.5 mcg/mL was defined as outside the therapeutic range and was set as the outcome of this study.
Results:
Among the 114 patients enrolled, 61 patients were included in the analysis. Oral administration of a maintenance dose of voriconazole and C-reactive protein (CRP) level were significantly and independently associated with a low initial trough concentration of voriconazole (<1.0 mcg/mL). Alanine aminotransferase levels were a significant factor associated with a high initial trough concentration of voriconazole (>5.5 mcg/mL) after adjusting for sex, age, weight, and serum creatinine (odds ratio 5.42; 95% confidence interval 1.34-21.97).
Conclusions:
Considering the variability of voriconazole concentrations in pediatric patients, monitoring certain parameters and considering the route of administration could help determine the therapeutic range of voriconazole and subsequently avoid unwanted effects.
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