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


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.
Luber
A D
AD
University of Pennsylvania, Philadelphia, PA, USA. a.luber@earthlink.net
Brower
R
R
Kim
D
D
Silverman
R
R
Peloquin
C A
CA
Frank
I
I
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D010755:Organophosphates / Q000008:administration & dosage / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D009842:Oligopeptides; D010755:Organophosphates; D054328:Proton Pump Inhibitors; D011725:Pyridines; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D009853:Omeprazole; C426859:fosamprenavir