title: Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity.
abstract: BACKGROUND
  Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.
  
  
  METHODS
  A 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. Voriconazole trough concentrations (C0) were within target range while the patient was under esomeprazole, a CYP2C19 inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping showed a variant allele associated with increased enzyme activity. The patient was switched to ranitidine because of the introduction of atazanavir. CYP3A4 inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed restoring voriconazole C0 back to target range.
  
  
  CONCLUSIONS
  The integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland ; Division of Nephrology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Bouatou
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland ; Swiss Centre for Applied Human Toxicology (SCAHT), Geneva, Switzerland.
authors.forename: Caroline Flora
authors.initials: CF
authors.lastname: Samer
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Kuntheavy Roseline
authors.initials: KR
authors.lastname: Ing Lorenzini
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland ; Swiss Centre for Applied Human Toxicology (SCAHT), Geneva, Switzerland.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Daali
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Samira
authors.initials: S
authors.lastname: Daou
authors.affiliation: Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Fathi
authors.affiliation: Division of Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Michela
authors.initials: M
authors.lastname: Rebsamen
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland ; Swiss Centre for Applied Human Toxicology (SCAHT), Geneva, Switzerland.
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
authors.affiliation: Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Calmy
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Monica
authors.initials: M
authors.lastname: Escher
keywords: CYP; Drug interaction; Individualization; Pharmacogenetics; Therapeutic drug monitoring; antifungal