Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients
Status:
Completed
Trial end date:
2011-01-01
Target enrollment:
Participant gender:
Summary
The licensed dose of raltegravir is 400 mg twice daily with or without food. Raltegravir is
metabolized predominantly through glucuronidation by UGT1A1. Atazanavir increases the plasma
concentrations of raltegravir 400 mg twice daily by 72% due to inhibition of UGT 1A1.
This suggests that combined use of atazanavir and a lower dose frequency of raltegravir, once
daily for example, is possible. Another reason why raltegravir most likely can be applied is
that its pharmacodynamic effect is not related to Cmin but to AUC which is expected to be
similar for an 800mg QD dose when compared to 400mg BD. Phase III clinical trials evaluating
QD dosing of raltegravir are currently ongoing and interim results are expected to be
published in mid 2009.
A regimen of atazanavir and raltegravir in combination with lamivudine or emtricitabine may
be a well tolerated and effective NNRTI-, and ritonavir-sparing regimen that could be an
attractive option for both first and second line (after NRTI/NNRTI failure) treatment
regimens.