title: Effect of efavirenz, nevirapine, etravirine, and raltegravir administration on the pharmacokinetics of ritonavir-boosted darunavir in a population of HIV-infected patients.
abstract: Abstract   The influence of efavirenz, etravirine, raltegravir, and nevirapine administration on the pharmacokinetics of ritonavir-boosted darunavir was investigated using population pharmacokinetics analysis. The population was composed of 142 patients infected with HIV: darunavir plus nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), 54 patients (group A); darunavir plus efavirenz±NRTI, 4 patients (group B); darunavir plus etravirine±NRTI, 5 patients (group C); darunavir plus nevirapine±NRTI, 21 patients (group D); darunavir plus raltegravir±NRTI, 38 patients (group E); and darunavir plus raltegravir and etravirine±NRTI, 20 patients (group F). A significant increase in darunavir clearance in combination with nevirapine (+66%) and efavirenz (+235%) was observed. A significant decrease (p<0.05) in trough plasma concentration was observed in groups B and D compared with the other groups. Our study indicates that the combination of ritonavir-boosted darunavir and etravirine or raltegravir has no significant influence on the pharmacokinetics of darunavir in contrast to the combination of ritonavir-boosted darunavir and nevirapine or efavirenz, which involves an increase in darunavir clearance and a decrease in the plasma concentration of darunavir.
authors.affiliation: Clinical Pharmacology Department, CHU de Nantes, Nantes, France. eric.dailly@chu-nantes.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Dailly
authors.forename: Clotilde
authors.initials: C
authors.lastname: Allavena
authors.forename: Regis
authors.initials: R
authors.lastname: Bouquié
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deslandes
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Pascale
authors.initials: P
authors.lastname: Jolliet
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use*; D003521:Cyclopropanes; D000069454:Darunavir; D004357:Drug Synergism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use*; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D013449:Sulfonamides; C451734:etravirine; D000068898:Raltegravir Potassium; D019829:Nevirapine; C098320:efavirenz; D019438:Ritonavir; D000069454:Darunavir