title: Boosted saquinavir hard gel formulation exposure in HIV-infected subjects: ritonavir 100 mg once daily versus twice daily.
abstract: OBJECTIVE
  The amount of ritonavir needed to enhance saquinavir hard gel (hg) plasma concentrations is unclear. Reduced ritonavir dosing may help to reduce ritonavir-related side effects and costs. This study examined the pharmacokinetics of twice-daily saquinavir-hg (1000 mg) in the presence of ritonavir 100 mg, dosed twice-daily and once-daily on one single occasion.
  
  
  METHODS
  Eighteen HIV-infected adults taking saquinavir/ritonavir 1000/100 mg twice-daily underwent pharmacokinetic (PK) assessment of saquinavir/ritonavir on day 1 following a morning saquinavir/ritonavir dose. On day 2, PK assessment was repeated when subjects took saquinavir without ritonavir. Drug intake (with a standard meal containing 20 g of fat) was timed on days -1, 1 and 2. Geometric mean ratios (GMR) and 95% confidence intervals (CI) were calculated to assess changes in saquinavir PK parameters.
  
  
  RESULTS
  Geometric mean saquinavir AUC(0-12), C(trough), C(max) and elimination half-life on days 1 and 2 were 14 389 and 9590 ng.h/mL, 331 and 234 ng/mL, 2503 and 1893 ng/mL and 2.80 and 2.82 h, respectively. The GMR (95% CI) for these parameters were 0.67 (0.53-0.84), 0.71 (0.48-1.04), 0.76 (0.58-0.98) and 1.01 (0.86-1.18), respectively.
  
  
  CONCLUSIONS
  Withholding a ritonavir dose significantly reduces overall saquinavir exposure and C(max), but had no impact on the elimination half-life. These data establish the need to administer saquinavir and ritonavir simultaneously.
authors.affiliation: PK Research Ltd, St Stephen's Centre, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. marta.boffito@chelwest.nhs.uk
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Desmond
authors.initials: D
authors.lastname: Maitland
authors.forename: Laura
authors.initials: L
authors.lastname: Dickinson
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Carl
authors.initials: C
authors.lastname: Fletcher
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
mesh_terms: D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D019438:Ritonavir / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019258:Saquinavir; D019438:Ritonavir