Barbara J. Brennan

Learn More
Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV(More)
There is an unmet need for an intravenous (i.v.) neuraminidase inhibitor, particularly for patients with severe influenza who cannot take oral medication. Two phase I pharmacokinetic and safety studies of i.v. oseltamivir were carried out in healthy volunteers. The first was an open-label, randomized, four-period, two-sequence, single-dose trial of 100 mg,(More)
BACKGROUND Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful(More)
The purpose of the present study was to assess the impact of age and gender on the pharmacokinetics (PK) of R667. Thirty six healthy male and female volunteers (12 m 18-45 years; 12 m and 12 f > or = 65 years) received a single 1 mg oral dose of R667. Serial blood samples were collected for determination of plasma R667 and metabolite concentrations. The PK(More)
Danoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a-ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a-ribavirin in(More)
BACKGROUND Viral kinetic models have proven useful to characterize treatment effectiveness during HCV therapy with interferon (IFN) or with direct-acting antivirals. METHODS We use a pharmacokinetic/viral kinetic (PK/VK) model to describe HCV RNA kinetics during treatment with danoprevir, a protease inhibitor. In a Phase I study, danoprevir monotherapy(More)
STUDY OBJECTIVE To investigate the steady-state pharmacokinetics of methadone when coadministered with ritonavir-boosted danoprevir (DNVr). DESIGN Open-label, two-period, single-sequence pharmacokinetic study. SETTING Two U.S. research centers. PATIENTS Eighteen methadone-maintained healthy adults. MEASUREMENTS AND MAIN RESULTS In Period 1 (Day -1),(More)
BACKGROUND Amongst Caucasian, Hispanic and African Americans with genotype 1 hepatitis C virus (HCV), there is a wide variation in response to treatment with peginterferon alfa-2a (PEG-IFN alfa-2a) and ribavirin. AIM To evaluate the pharmacokinetics (PK) of PEG-IFN alfa-2a and ribavirin among these three groups. METHODS Forty-seven patients with(More)
BACKGROUND Interferon (IFN)-based therapy is the recommended treatment for hepatitis C virus. Because pegylated IFN (PEG-IFN) alfa-2a is administered subcutaneously, it is of interest to determine the proportion of the dose that is absorbed from the subcutaneous (SC) tissue and ultimately reaches systemic circulation. OBJECTIVE The goal of this study was(More)
The purpose of this study was to investigate the potential for a CYP3A4-mediated drug interaction between R667 and midazolam (MDZ) in healthy subjects. R667 is metabolized by CYP3A4 and therefore may interact with CYP3A4 substrates. In the present study, 18 healthy male subjects received a single 15-mg oral dose of MDZ with and without R667(More)