All other possibly drug-related AEs (ie, asthenia, fatigue, and palpitations) were reported once. In addition, five AEs were reported

by five subjects in cohort B, all of which were of mild intensity. Two AEs were considered possibly drug-related (dysgeusia, n = 1; headache, n = 1; both after boceprevir-only treatment). There is a significant unmet clinical need for the treatment of recurrent hepatitis C after liver transplantation. SVR rates for patients receiving PEG-IFNα and Ruxolitinib cell line ribavirin after liver transplantation are low, with less than one-third of patients achieving SVR.11 Furthermore, treatment-related toxicity represents a significant barrier to completion of therapy.12 Thus, the liver transplantation population

represents a subgroup of patients with chronic hepatitis C who could potentially derive significant clinical benefit from the use of direct-acting antiviral agents. Calcineurin inhibitors, such as cyclosporine and tacrolimus, are routinely administered in these patients as immunosuppressants to prevent allograft rejection. selleck inhibitor Given the narrow therapeutic index within which these agents are effective, and the subsequent need for therapeutic Methane monooxygenase monitoring, a clear and detailed understanding of their propensity for drug-drug interactions is required

before their concomitant use with new pharmacologic agents. Cyclosporine and tacrolimus are both substrates of CYP3A4/5. Because boceprevir is a strong inhibitor of CYP3A4, coadministration with boceprevir would be anticipated to increase exposure to these calcineurin inhibitors. The doses of cyclosporine (100 mg) and tacrolimus (0.5 mg) used in this study were optimized for investigation of the potential for drug-drug interactions between the individual drugs and boceprevir without jeopardizing subject safety. Consequently, doses were much lower (tacrolimus) than or at the lower end (cyclosporine) of standard therapeutic dosing in order to maintain a safety margin if significant elevations in immunosuppressant concentrations were observed upon boceprevir coadministration. In addition, cyclosporine and tacrolimus were each given as single doses to mitigate potential safety concerns (eg, those associated with accumulation). Boceprevir was dosed to steady state in order to ensure that the maximum inhibitory potential of the drug was assessed.