title: Invasive Aspergillus infection requiring lobectomy in a CYP2C19 rapid metabolizer with subtherapeutic voriconazole concentrations.
abstract: Individuals who carry the CYP2C19*17 gain-of-function allele have lower voriconazole exposure and are therefore at risk of failing therapy. Utilizing CYP2C19 genotype to optimize voriconazole dosage may be a cost-effective method of improving treatment outcomes. However, there are limited data describing what initial voriconazole dosage should be used in those with increased CYP2C19 metabolic capacity. Herein, we present a case report of a pediatric CYP2C19 rapid metabolizer (i.e., CYP2C19*1/*17) requiring a voriconazole dosage of 14 mg/kg twice daily (usual pediatric dosage ranges from 7 to 9 mg/kg twice daily). This case report supports the clinical utility of using CYP2C19 genotype to guide voriconazole dosing, and provides data for establishing an initial voriconazole dose in pediatric CYP2C19 rapid metabolizers.
authors.affiliation: Pharmacy Department, Cleveland Clinic, Cleveland, OH, USA.|Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Hicks
authors.affiliation: Medicine Institute, Infectious Disease Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Gonzalez
authors.affiliation: Pharmacy Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Zembillas
authors.affiliation: Pharmacy Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Karissa
authors.initials: K
authors.lastname: Kusick
authors.affiliation: Heart & Vascular Institute, Thoracic & Cardiovascular Surgery Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Sudish
authors.initials: S
authors.lastname: Murthy
authors.affiliation: Heart & Vascular Institute, Thoracic & Cardiovascular Surgery Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Siva
authors.initials: S
authors.lastname: Raja
authors.affiliation: Medicine Institute, Infectious Disease Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Gordon
authors.affiliation: Children's Hospital & Pediatrics Institute, Hematology & Oncology Department, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Rabi
authors.initials: R
authors.lastname: Hanna
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D000071184:Pharmacogenomic Variants; D057285:Precision Medicine; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000628:therapy; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole
keywords: CYP2C19; personalized medicine; pharmacogenomics; precision medicine; therapeutic drug monitoring; voriconazole