Drug
Interactions between Brecanavir and other HIV Protease Inhibitors Brecanavir
(BCV) is a potent HIV protease inhibitor (PI), currently in Phase II development.
Chronic doses of BCV (150mg, 300mg, and 600mg)/RTV 100mg q12h are under study
in treatment-experienced HIV patients. The current studies provide an overview
of BCV drug interactions with other ritonavir (RTV)-boosted PIs.
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 are shown in the following chart:
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.
The authors conclude, “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.” GlaxoSmithKline,
Research Triangle Park, USA. 8/15/06 Reference M
J Shelton, S Ford, M T Anderson, and others. Overview of drug interactions between
brecanavir (BCV) and other HIV protease inhibitors (PIs). 16th International AIDS
Conference. August 13-18, 2006. Toronto, Canada. Abstract TUAB0105 
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