title: Ritonavir boosting dose reduction from 100 to 50 mg does not change the atazanavir steady-state exposure in healthy volunteers.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics, tolerability and safety of 300 mg of atazanavir boosted with 100 or 50 mg of ritonavir, both once daily, at steady state.
  
  
  METHODS
  This was a single-blind, multiple-dose, crossover, sequence-randomized trial. Thirteen healthy HIV-1-negative men received witnessed once-daily doses of atazanavir (300 mg) and 100 or 50 mg of ritonavir for 10 days (15 day washout). Atazanavir and ritonavir plasma concentrations were determined for 24 h on day 10. Log-transformed individual pharmacokinetic parameters were compared between treatments (analysis of variance); the difference between treatments on the log scale and 95% CIs were calculated. Fasting cholesterol, triglycerides, glucose and bilirubin plasma levels were measured at the beginning and end of each period and compared (Wilcoxon signed rank test). Gastrointestinal symptoms and other events were recorded.
  
  
  RESULTS
  Ritonavir C(max) and the AUC₀₋₂₄ were lower after the 50 mg booster dose than after 100 mg [geometric mean ratio (GMR) (95% CI), 0.40 (0.31-0.51) and 0.35 (0.29-0.42), respectively]. No differences were observed in atazanavir exposure with 50 or 100 mg of ritonavir [GMR C(max) (95% CI), 1.00 (0.79-1.28); GMR AUC₀₋₂₄ (95% CI), 0.98 (0.79-1.21)]. Atazanavir trough concentration was >0.15 mg/L in all volunteers. Total and low-density lipoprotein cholesterol increased 0.40 mM (P = 0.01) and 0.37 mM (P = 0.003) from their corresponding baseline value during the 100 mg dosing period; there were no significant changes on 50 mg. Mild increases in bilirubin were detected on day 10 after both treatments without differences between treatments.
  
  
  CONCLUSIONS
  In spite of higher exposure to ritonavir with 100 mg, atazanavir exposure was equivalent; the lipid profile was better under the lower booster dose (50 mg).
authors.affiliation: Pharmacokinetic/Pharmacodynamic Modelling and Simulation,  Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau-IIB Sant Pau, Barcelona,  Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Estévez
authors.forename: José
authors.initials: J
authors.lastname: Moltó
authors.forename: Laura
authors.initials: L
authors.lastname: Tuneu
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeño
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Antonijoan
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mangues
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Montse
authors.initials: M
authors.lastname: Puntes
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Barbanoj
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D008055:Lipids; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir