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

• Published in: HIV medicine Vol. 8; no. 7; pp. 457 - 464
• Main Authors: Luber, AD, Brower, R, Kim, D, Silverman, R, Peloquin, CA, Frank, I
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Area Under Curve; atazanavir; Atazanavir Sulfate; Carbamates - administration & dosage; Carbamates - pharmacokinetics; Drug Therapy, Combination; Female; fosamprenavir; HIV Infections - drug therapy; Humans; Male; Oligopeptides - administration & dosage; Oligopeptides - pharmacokinetics; omeprazole; 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
• ISSN: 1464-2662; 1468-1293
• 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.