Pharmacokinetic interaction between the hepatitis C virus protease inhibitor boceprevir and cyclosporine and tacrolimus in healthy volunteers

• DOI: 10.1002/hep.25831
• Publication Date: 2012-05-11T09:55:48Z
• Authors: Ellen Hulskotte; Samir Gupta; Fengjuan Xuan; Marga van Zutven; Edward O'Mara; Hwa-Ping Feng; John Wagner; Joan Butterton
• Keywords: Boceprevir; Concomitant

The hepatitis C virus protease inhibitor boceprevir is a strong of cytochrome P450 3A4 and 3A5 (CYP3A4/5). Cyclosporine tacrolimus are calcineurin immunosuppressants used to prevent organ rejection after liver transplantation; both substrates CYP3A4. This two-part pharmacokinetic interaction study evaluated with cyclosporine (part 1) 2). In part 1, 10 subjects received single-dose (100 mg) on day (800 3, concomitant cyclosporine/boceprevir 4. After washout, mg three times day) for 7 days plus 6. 2A, 12 (0.5 mg). they 11 2B, 24 hours later Coadministration cyclosporine/tacrolimus was well tolerated. Concomitant increased the area under concentration-time curve from time 0 infinity single dosing (AUC(inf) ) maximum observed plasma (or blood) concentration (C(max) geometric mean ratios (GMRs) (90% confidence interval [CI]) 2.7 (2.4-3.1) 2.0 (1.7-2.4), respectively. AUC(inf) C(max) GMRs CI) 17 (14-21) 9.9 (8.0-12), Neither nor coadministration had meaningful effect pharmacokinetics.Dose adjustments should be anticipated when administered boceprevir, guided by close monitoring blood concentrations frequent assessments renal function cyclosporine-related side effects. Administration requires significant dose reduction prolongation tacrolimus, tacrolimus-related