title: Co-administration of raltegravir reduces daily darunavir exposure in HIV-1 infected patients.
abstract: The potential drug-to-drug interaction between darunavir and raltegravir in the setting of HIV infection is a highly debated issue still unresolved. In the present study we have evaluated the pharmacokinetics of darunavir and ritonavir in 53 HIV-1 infected patients with or without concomitant raltegravir administration. The assessment of trough plasma drug concentrations was carried out in all subjects and the potential influence of raltegravir on darunavir and ritonavir disposition, assessed by specific pharmacokinetic evaluations in a subgroup of 25 patients. No significant differences on darunavir and ritonavir plasma trough levels were observed between patients receiving or not raltegravir. Co-administration of raltegravir was, however, associated with a 40% reduction in darunavir C(max) and estimated AUC(0-24), as well a 60% increase in the estimated darunavir clearance compared with values measured in patients not given raltegravir. Notably, this interaction was independent of the dosage of darunavir and not due to effects of raltegravir on the pharmacokinetics of ritonavir. These results should be taken into account when darunavir-based regimens are implemented in the setting of HIV, especially considering that this drug is usually administered at fixed daily dose and no therapeutic drug monitoring is performed in most centres.
authors.affiliation: Unit of Clinical Pharmacology, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Dept. of Clinical Sciences L. Sacco, University Hospital Luigi Sacco, Università di Milano, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Cristina
authors.initials: C
authors.lastname: Gervasoni
authors.forename: Valeria
authors.initials: V
authors.lastname: Cozzi
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.forename: Serena
authors.initials: S
authors.lastname: Fucile
authors.forename: Paola
authors.initials: P
authors.lastname: Meraviglia
authors.forename: Simona
authors.initials: S
authors.lastname: Landonio
authors.forename: Gabriella
authors.initials: G
authors.lastname: Boreggio
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
mesh_terms: D000328:Adult; D000069454:Darunavir; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D013449:Sulfonamides; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir