Steady-state pharmacokinetics of once-daily fosamprenavir/ritonavir and atazanavir/ritonavir alone and in combination with 20 mg omeprazole in healthy volunteers

HIV Med. 2007 Oct;8(7):457-64. doi: 10.1111/j.1468-1293.2007.00496.x.


Objectives: Use of proton pump inhibitors in HIV-infected patients is common. The purpose of this study was to determine the steady-state pharmacokinetics of once-daily (qd) fosamprenavir/ritonavir (FPV/r) and atazanavir/ritonavir (ATV/r) alone and in combination with 20 mg qd omeprazole (OMP) in healthy volunteers.

Design and methods: A prospective, open-label, single-site, two-period, crossover pharmacokinetic study was carried out in healthy volunteers. Subjects received either qd FPV/r 1400 mg/200 mg or ATV/r 300 mg/100 mg in the morning for 14 days and then 20 mg OMP in the evening for an additional 7 days. The pharmacokinetics were assessed over 24 h on days 14 and 21. Following a 2-week washout, subjects repeated the process with the other regimen. Trough protease inhibitor (PI) concentrations were taken on day 16 of each period to assess the impact of a single dose of OMP on ATV and amprenavir (APV) concentrations. Plasma ATV and APV pharmacokinetic parameters were assessed by noncompartmental analysis; geometric mean ratios (GMRs; PI+OMP/PI; 90% confidence interval) were calculated between days 14 and 21.

Results: Nineteen healthy, non-HIV-infected volunteers were evaluated. OMP reduced ATV exposure [area under the concentration curve at 0-24 h (AUC0-24 h)] and the minimum drug concentration (Cmin) by 27% each. In contrast, APV exposure and Cmin were decreased by 4 and 2%, respectively. Four subjects (21%) experienced greater than 50% declines in both ATV AUC0-24 h and Cmin after the addition of OMP; this was not observed in any subject following receipt of FPV/r. No alterations in APV or ATV trough concentrations were observed following a single dose of OMP.

Conclusions: The addition of 20 mg OMP administered in the evening has minimal effect on APV pharmacokinetics. In contrast, ATV pharmacokinetics were altered; a number of ATV-treated subjects experienced pronounced declines in exposures upon the addition of 20 mg OMP administered in the evening, whereas others experienced little to no change.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • Area Under Curve
  • Atazanavir Sulfate
  • Carbamates / administration & dosage
  • Carbamates / pharmacokinetics
  • Drug Therapy, Combination
  • Female
  • Furans
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacokinetics
  • Omeprazole / administration & dosage
  • Omeprazole / pharmacokinetics
  • Organophosphates / administration & dosage
  • Organophosphates / pharmacokinetics
  • Proton Pump Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / pharmacokinetics
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacokinetics


  • Anti-HIV Agents
  • Carbamates
  • Furans
  • Oligopeptides
  • Organophosphates
  • Proton Pump Inhibitors
  • Pyridines
  • Sulfonamides
  • Atazanavir Sulfate
  • Omeprazole
  • fosamprenavir