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Steady‐state pharmacokinetics of once‐daily fosamprenavir/ritonavir and atazanavir/ritonavir alone and in combination with 20 mg omeprazole in healthy volunteers *
Author(s) -
Luber AD,
Brower R,
Kim D,
Silverman R,
Peloquin CA,
Frank I
Publication year - 2007
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2007.00496.x
Subject(s) - cmin , pharmacokinetics , ritonavir , amprenavir , medicine , pharmacology , crossover study , lopinavir , atazanavir , trough concentration , cmax , omeprazole , area under the curve , viral load , human immunodeficiency virus (hiv) , chemistry , virology , placebo , antiretroviral therapy , protease , pathology , hiv 1 protease , biochemistry , alternative medicine , enzyme
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 (AUC 0–24 h )] and the minimum drug concentration ( C min ) by 27% each. In contrast, APV exposure and C min were decreased by 4 and 2%, respectively. Four subjects (21%) experienced greater than 50% declines in both ATV AUC 0–24 h and C min 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.