|
|
Abstract
Bioequivalence of the co-formulation of efavirenz /emtricitabine/tenofovir DF
A. Mathias, A. Plummer, J. Skillington, J. Hui, J. Hinkle, K. Yale, B. Kearney
Background: Efavirenz (EFV; 600 mg), emtricitabine (FTC; 200 mg) and tenofovir DF (TDF; 300 mg) are preferred agents for use in the treatment of HIV-1. This study evaluated the pharmacokinetics (PK) and bioequivalence of an investigational co-formulation of EFV/FTC/TDF (Test) to their commercially available individual dosage forms (EFV+FTC+TDF, Reference) in a single-dose study in healthy subjects.
Methods: Subjects were randomized to two treatment sequences in an open-label cross-over study design. Study drugs were administered under fasted conditions. Serial blood samples were obtained over 504 hours after oral administration of each treatment and pk parameters calculated using noncompartmental methods. Formulation bioequivalence was assessed by 90% confidence intervals (CI) for the ratio of geometric least square means (GMR) for Cmax, AUC0-t, and AUCinf for the Test versus Reference treatment.
Results: 48 subjects were enrolled and 45 completed the study. Headache and dizziness was reported as the most frequent drug-related adverse events in 24.4% (Test) to 29.2 % (Reference) of subjects. Arithmetic mean (CV %) and the GMR (90%CI) of the pk parameters for EFV, FTC and tenofovir (TFV) are presented below:
| | EFV | FTC | TFV | | PK Parameter | Test | Reference | %GMR (90%CI) | Test | Reference | %GMR (90%CI) | Test | Reference | %GMR (90%CI) | | Cmax (mg/mL) | 2.28 (26.7) | 2.30 (30.6) | 99.9 (93.4,107) | 2.13 (25.3) | 2.38 (20.4) | 88.8 (84.0,93.9) | 0.325 (34.2) | 0.353 (29.6) | 91.5 (84.6,98.8) | | AUC0-t (mg.hr/mL) | 125 (25.9) | 133 (27.3) | 95.7 (90.5,101) | 10.7 (18.1) | 10.9 (14.9) | 98.0 (94.9,101) | 1.95 (32.9) | 1.97 (32.8) | 99.3 (91.0,108) | | AUCinf (mg.hr/mL) | 144 (32.0) | 155 (35.1) | 95.2 (88.9,102) | 10.9 (17.9) | 11.1 (14.9) | 98.0 (94.9,101) | 2.31 (29.2) | 2.32 (30.3) | 100 (93.2,108) |
Conclusions: The co-formulation of EFV/FTC/TDF is bioequivalent to administration of its individual components and represents the first one pill, once-daily complete antiretroviral regimen for the treatment of HIV 1 infection.
AIDS 2006 - XVI International AIDS Conference
Abstract no.
TUPE0098
Suggested Citation
"A.Mathias, et al.
Bioequivalence of the co-formulation of efavirenz /emtricitabine/tenofovir DF.
:
AIDS 2006 - XVI International AIDS Conference:
Abstract no.
TUPE0098"
|
|
|