Pharmacokinetics of atazanavir/ritonavir once daily and lopinavir/ritonavir twice and once daily over 72 h following drug cessation.
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.
Boffito
Marta
M
St. Stephen's Centre, Chelsea and Westminster Hospital, London, UK. marta.boffito@chelwest.nhs.uk
Else
Laura
L
Back
David
D
Taylor
Jessica
J
Khoo
Saye
S
Sousa
Marta
M
Pozniak
Anton
A
Gazzard
Brian
B
Moyle
Graeme
G
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000069446:Atazanavir Sulfate; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir