BACKGROUND: We investigated the pharmacokinetics of atazanavir/ritonavir once daily and lopinavir/ritonavir twice and once daily over 72 h following drug intake cessation. METHODS: This was an open-label, three-session, pharmacokinetic trial. Healthy volunteers received atazanavir/ritonavir 300/100 mg once daily and lopinavir/ritonavir 400/100 mg twice daily and 800/200 mg once daily separately for 10 days. Pharmacokinetic profiles were assessed for each phase on day 10 over 72 h. Pharmacokinetic parameters were determined over 12 or 24 h and to the last measurable concentration by non-compartmental methods. RESULTS:Sixteen participants completed the study. Geometric mean terminal elimination half-life to 72 h of atazanavir was 8.35 h and not different from the 0-24 h half-life (9.91 h). Terminal elimination halflife of lopinavir was 2.33 h (twice daily) and 2.44 h (once daily). These values were lower compared with the half-life over the respective dosing intervals (7.15 and 4.88 h for 0-12 and 0-24 h, respectively). No participant on atazanavir had concentrations below the minimum effective concentration (MEC) of 150 ng/ml at 24 h. In total, 44% of the participants on lopinavir once daily had concentrations below the MEC of 1,000 ng/ml at 24 h. At 16 h and 20 h, 13% and 63% of participants were below target for twice daily lopinavir, respectively. At 36 h, all participants on lopinavir and 31% on atazanavir were below target. Ritonavir area under the plasma concentration-time curve was 30% lower and 26% higher when dosed at 100 mg or 200 mg with lopinavir versus atazanavir. CONCLUSIONS: This study investigated the pharmacokinetic forgiveness of two boosted protease inhibitors. Whereas the decline in lopinavir concentrations occured rapidly as the boosting effect of ritonavir diminished, the rate of decline of atazanavir remained constant to 72 h.
RCT Entities:
BACKGROUND: We investigated the pharmacokinetics of atazanavir/ritonavir once daily and lopinavir/ritonavir twice and once daily over 72 h following drug intake cessation. METHODS: This was an open-label, three-session, pharmacokinetic trial. Healthy volunteers received atazanavir/ritonavir 300/100 mg once daily and lopinavir/ritonavir 400/100 mg twice daily and 800/200 mg once daily separately for 10 days. Pharmacokinetic profiles were assessed for each phase on day 10 over 72 h. Pharmacokinetic parameters were determined over 12 or 24 h and to the last measurable concentration by non-compartmental methods. RESULTS: Sixteen participants completed the study. Geometric mean terminal elimination half-life to 72 h of atazanavir was 8.35 h and not different from the 0-24 h half-life (9.91 h). Terminal elimination halflife of lopinavir was 2.33 h (twice daily) and 2.44 h (once daily). These values were lower compared with the half-life over the respective dosing intervals (7.15 and 4.88 h for 0-12 and 0-24 h, respectively). No participant on atazanavir had concentrations below the minimum effective concentration (MEC) of 150 ng/ml at 24 h. In total, 44% of the participants on lopinavir once daily had concentrations below the MEC of 1,000 ng/ml at 24 h. At 16 h and 20 h, 13% and 63% of participants were below target for twice daily lopinavir, respectively. At 36 h, all participants on lopinavir and 31% on atazanavir were below target. Ritonavir area under the plasma concentration-time curve was 30% lower and 26% higher when dosed at 100 mg or 200 mg with lopinavir versus atazanavir. CONCLUSIONS: This study investigated the pharmacokinetic forgiveness of two boosted protease inhibitors. Whereas the decline in lopinavir concentrations occured rapidly as the boosting effect of ritonavir diminished, the rate of decline of atazanavir remained constant to 72 h.
Authors: Laura Dickinson; Marta Boffito; David Back; Laura Else; Nils von Hentig; Geraint Davies; Saye Khoo; Anton Pozniak; Graeme Moyle; Leon Aarons Journal: Antimicrob Agents Chemother Date: 2011-03-21 Impact factor: 5.191
Authors: Dongning Wang; Charles B Hicks; Neela D Goswami; Emi Tafoya; Ruy M Ribeiro; Fangping Cai; Alan S Perelson; Feng Gao Journal: J Virol Date: 2011-04-13 Impact factor: 5.103
Authors: Akil Jackson; Andrew Hill; Rebekah Puls; Laura Else; Janaki Amin; David Back; Enmoore Lin; Saye Khoo; Sean Emery; Roland Morley; Brian Gazzard; Marta Boffito Journal: J Antimicrob Chemother Date: 2010-12-17 Impact factor: 5.790
Authors: Alessandro Schipani; Deirdre Egan; Laura Dickinson; Gerry Davies; Marta Boffito; Mike Youle; Saye H Khoo; David J Back; Andrew Owen Journal: Antivir Ther Date: 2012-04-04
Authors: Laura Dickinson; Marta Boffito; David Back; Laura Waters; Laura Else; Geraint Davies; Saye Khoo; Anton Pozniak; Leon Aarons Journal: J Antimicrob Chemother Date: 2009-03-28 Impact factor: 5.790