title: Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers.
abstract: BACKGROUND
  Recent studies have described reduced absorption of certain protease inhibitors when administered with agents known to increase gastric pH. No clinically significant interactions between saquinavir absorption and gastric pH have previously been shown. We evaluated the effect of omeprazole, a proton-pump-inhibitor, on the pharmacokinetics of the recently developed saquinavir-500 mg formulation co-administered with ritonavir.
  
  
  METHODS
  Eighteen healthy subjects (n = 6 women and 12 men) received 1000/100 mg saquinavir/ritonavir twice daily in an open-label study for 15 days. On days 11-15, subjects were administered omeprazole 40 mg daily with the morning dose. Serial plasma samples were collected for 12-h pharmacokinetic profiles of saquinavir and ritonavir on days 10 and 15 and safety analysis on days 1, 4, 10, 15 and 29.
  
  
  RESULTS
  The geometric mean and 95% confidence interval (CI), for the area under time-concentration curve (AUC; ng h/ml), trough plasma concentration (C trough; ng/ml) and maximum observed plasma concentration (Cmax; ng/ml) of saquinavir were 20599 (14396-29360) and 37511 (28733-48970); 737 (482-1127) and 1521 (1039-2227); 3227 (2370-4393) and 5611 (4507-7710) on days 10 and 15, respectively, with geometric mean ratios of 1.82, 2.06 and 1.75. No significant changes were observed in saquinavir elimination half life, ritonavir pharmacokinetic parameters or in safety laboratory tests. No unexpected adverse events attributed to study medication were noted.
  
  
  CONCLUSIONS
  In the presence of omeprazole, total saquinavir plasma exposure is significantly increased (82% increase in AUC). The mechanism of this interaction requires elucidation. Despite the significant increase in saquinavir exposure, no short term toxicities were observed.
authors.affiliation: Chelsea and Westminster Hospital, London, UK. awinston@imperial.ac.uk
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Carl
authors.initials: C
authors.lastname: Fletcher
authors.forename: Lesley
authors.initials: L
authors.lastname: Robinson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Unsworth
authors.forename: Izabela
authors.initials: I
authors.lastname: Tolowinska
authors.forename: Malte
authors.initials: M
authors.lastname: Schutz
authors.forename: Anton L
authors.initials: AL
authors.lastname: Pozniak
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
mesh_terms: D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D019438:Ritonavir / Q000097:blood; D019258:Saquinavir / Q000097:blood*
chemical_list: D000897:Anti-Ulcer Agents; D017320:HIV Protease Inhibitors; D054328:Proton Pump Inhibitors; D009853:Omeprazole; D019258:Saquinavir; D019438:Ritonavir