Dataset Information

Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes.

ABSTRACT:

Aim

Our objective was to describe the association between voriconazole concentrations and CYP2C19 diplotypes in pediatric cancer patients, including children homozygous for the CYP2C19*17 gain-of-function allele.

Materials & methods

A linear mixed effect model compared voriconazole dose-corrected trough concentrations (n = 142) among CYP2C19 diplotypes in 33 patients (aged 1-19 years). Voriconazole pharmacokinetics was described by a two-compartment model with Michaelis-Menten elimination.

Results

Age (p = 0.05) and CYP2C19 diplotype (p = 0.002) were associated with voriconazole concentrations. CYP2C19*17 homozygotes never attained therapeutic concentrations, and had lower dose-corrected voriconazole concentrations (median 0.01 μg/ml/mg/kg; p = 0.02) than CYP2C19*1 homozygotes (median 0.07 μg/ml/mg/kg). Modeling indicates that higher doses may produce therapeutic concentrations in younger children and in those with a CYP2C19*17/*17 diplotype.

Conclusion

Younger age and the presence of CYP2C19 gain-of-function alleles were associated with subtherapeutic voriconazole concentrations. Starting doses based on age and CYP2C19 status could increase the number of patients achieving therapeutic voriconazole exposure.

SUBMITTER: Hicks JK

PROVIDER: S-EPMC4155516 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes.

Hicks J Kevin JK Crews Kristine R KR Flynn Patricia P Haidar Cyrine E CE Daniels Calvin C CC Yang Wenjian W Panetta John C JC Pei Deqing D Scott Jeffrey R JR Molinelli Alejandro R AR Broeckel Ulrich U Bhojwani Deepa D Evans William E WE Relling Mary V MV

Pharmacogenomics 20140601 8

<h4>Aim</h4>Our objective was to describe the association between voriconazole concentrations and CYP2C19 diplotypes in pediatric cancer patients, including children homozygous for the CYP2C19*17 gain-of-function allele.<h4>Materials & methods</h4>A linear mixed effect model compared voriconazole dose-corrected trough concentrations (n = 142) among CYP2C19 diplotypes in 33 patients (aged 1-19 years). Voriconazole pharmacokinetics was described by a two-compartment model with Michaelis-Menten eli ...[more]

PMID: 25084200

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Dataset Information

Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes.

Aim

Materials & methods

Results

Conclusion

Publications

Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes.

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