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Abstract
Overview of drug interactions between brecanavir (BCV) and other HIV protease inhibitors (PIs)
M.J. Shelton, S. Ford, M.T. Anderson, S. Murray, J. Ng-Cashin
Background: BCV is a potent PI, currently in Phase II development. Chronic doses of BCV (150mg, 300mg, and 600mg)/RTV 100mg q12h are currently under investigation in treatment-experienced HIV patients. An overview of BCV drug interactions with other RTV-boosted PIs is provided.
Methods: Three multiple-dose drug interaction studies were conducted in healthy adults. In Study 1, BCV 300mg q12h was administered with lopinavir/ritonavir (LPV/r) 400mg/100mg q12h and compared to BCV 300mg/RTV 100mg q12h or LPV/r q12h. In Study 2, BCV 300mg/RTV 100mg q12h was administered with atazanavir (ATV) 300mg q24h and compared to BCV 300mg/RTV 100mg q12h or ATV 300mg/RTV 100mg q24h. In Study 3, BCV 600mg/RTV 100mg q12h was given alone in Period 1, followed by BCV 600mg/RTV 200mg q12h or BCV 600mg/RTV 200mg + tipranavir (TPV) 500mg q12h in Period 2. Plasma concentrations of PIs were determined by LC/MS/MS and PK parameters were compared by ANOVA.
Results: Change in PK parameters for BCV/PI combinations
| Study | Analyte | AUC(0-t) | Cmax | Ct | | 1 | BCV | ¯16%
(¯7-25%) | « | ¯16%
(↑2%-¯17%) | | 1 | LPV | « | « | « | | 2 | BCV | ↑38%
(↑25-53%) | ↑48%
(↑29-71%) | ↑44%
(↑25-65%) | | 2 | ATV | ↑44%
(↑32-58%) | ↑21%
(↑12-30%) | ↑111%
(↑81-145%) |
In Study 3, combination dosing of BCV/RTV + TPV was discontinued prior to collection of steady-state pharmacokinetic data due to asymptomatic hepatic transaminase elevations (all Grades 1-2, except one subject with Grade 3-4). All elevations returned to baseline after discontinuation of study drugs.
Conclusions: BCV exposure was slightly reduced and LPV was unaffected following coadministration with LPV/r. Exposure to both BCV and ATV were increased following coadministration with ATV/RTV. BCV should not be coadministered with TPV/RTV. BCV appears to have a generally favorable drug interaction profile with LPV/r and ATV, such that significant reductions in plasma exposure are not apparent.
AIDS 2006 - XVI International AIDS Conference
Abstract no.
TUAB0105
Suggested Citation
"M.J.Shelton, et al.
Overview of drug interactions between brecanavir (BCV) and other HIV protease inhibitors (PIs).
Oral abstract session:
AIDS 2006 - XVI International AIDS Conference:
Abstract no.
TUAB0105"
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