title: Voriconazole and atazanavir: a CYP2C19-dependent manageable drug-drug interaction.
abstract: OBJECTIVE
  To investigate the pharmacokinetics of voriconazole when administered to HIV-positive patients receiving treatment with atazanavir-containing therapies according to CYP2C19 genotype.
  
  
  METHODS
  We describe four HIV-positive patients with pulmonary aspergillosis treated with voriconazole and atazanavir-based regimens (with or without ritonavir). They were managed by assessing their CYP2C19 genotype (CYP2C19*2, rs4244285, G>A, real-time PCR) and therapeutic drug monitoring (HPLC-based validation methods).
  
  
  CONCLUSIONS
  Voriconazole exposure was variable but Ctrough levels were above 1000 ng/ml in all patients; one CYP2C19 intermediate metabolizer required lower doses of voriconazole (50 mg twice daily) to obtain satisfactory drug concentrations. Atazanavir and ritonavir plasma levels were moderately reduced (area under the curve: -23 and -26%, respectively); raltegravir exposure seemed increased by voriconazole administration (area under the curve: 2.5-fold higher) in a single subject. Coadministration of atazanavir and voriconazole may be feasible in selected HIV-positive patients; therapeutic drug monitoring and CYP2C19 genotyping may optimize exposure of both drugs.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcagno
authors.forename: Lorena
authors.initials: L
authors.lastname: Baietto
authors.forename: Nicole
authors.initials: N
authors.lastname: Pagani
authors.forename: Marco
authors.initials: M
authors.lastname: Simiele
authors.forename: Sabrina
authors.initials: S
authors.lastname: Audagnotto
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: De Rosa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
mesh_terms: D000328:Adult; D000368:Aged; D000069446:Atazanavir Sulfate; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004347:Drug Interactions / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055732:Pulmonary Aspergillosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole; D019438:Ritonavir
keywords: HIV; antifungal; aspergillosis; drug–drug interactions; raltegravir; therapeutic drug monitoring