From CROI: Clinical Pharmacology of Boceprevir: Metabolism, Excretion, and Drug-Drug Interactions

(Jules Levin of NATAP.org reports on a session at CROI looking at Boceprevir drug interactions. Fortunately, with the notable exception of Efavirenz, it looks like BOC is a pretty clean drug in terms of DDI's)

Clinical Pharmacology of Boceprevir: Metabolism, Excretion, and Drug-Drug Interactions - see attached full slide report

Reported by Jules Levin

CROI – March 1, 2011
Boston, MA

C Kasserra, E Hughes, M Treitel,
S Gupta, and E O'Mara


AUTHOR CONCLUSIONS
•Radiolabeled data support a primarily hepatic-mediated clearance of BOC
•CYP3A4 probes
–Marked ↑ in midazolam exposure in the presence of BOC indicates that BOC is a strong, reversible inhibitor of CYP3A4
–↑ exposure to BOC with ketoconazole suggests involvement of another non–CYP3A4-mediated pathway
•Metabolic inhibitors (even in combination) did not alter BOC PK profile substantially to change BOC’s dose or schedule
–Diflunisal (AKR inhibitor) did not alter BOC exposure
–Ritonavir (CYP 3A4 inhibitor) did not substantively affect exposure to BOC
–Clarithromycin (CYP3A4, P-gp inhibitor) did not affect exposure to BOC
•No dosage adjustment is needed for the coadministration of BOC with tenofovir or peginterferon
•Clinical implications of a ↓ mean BOC trough concentration when coadministered with efavirenz will be clearer as data from coinfected populations are obtained
•Boceprevir did not affect the exposure to drospirenone/ ethinylestradiol in a manner that would be anticipated to reduce contraceptive efficacy