• Andrea Calcagno, Lorena Baietto, Nicole Pagani, Marco Simiele, Sabrina Audagnotto, Antonio D'Avolio, Francesco Giuseppe De Rosa, Giovanni Di Perri, and Stefano Bonora.
• Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy.
• Pharmacogenomics. 2014 Jul 1; 15 (10): 1281-6.

AimTo investigate the pharmacokinetics of voriconazole when administered to HIV-positive patients receiving treatment with atazanavir-containing therapies according to CYP2C19 genotype.Materials & MethodsWe 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).Results & ConclusionVoriconazole 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.

42 keywords...

hide…