학술논문

Hepatic Pharmacokinetics and Pharmacodynamics With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir Treatment and Variable Ribavirin Dosage.
Document Type
Journal Article
Source
Journal of Infectious Diseases. Feb2018, Vol. 217 Issue 3, p474-482. 9p.
Subject
*Hepatitis C treatment
*Needle biopsy
*Pharmacokinetics
*Pharmacodynamics
*Ribavirin
*Drug dosage
*RNA analysis
*Antiviral agents
*Blood plasma
*Combination drug therapy
*Drug side effects
*Hepatitis viruses
*Liver
*Research funding
*Statistical sampling
*Viral load
*Randomized controlled trials
*Treatment effectiveness
*Chronic hepatitis C
*Genotypes
Language
ISSN
0022-1899
Abstract
Background: It is unknown whether ribavirin (RBV) coadministration modifies the early rate of decline of hepatitis C virus (HCV) RNA in the liver versus plasma compartments, specifically.Methods: This partially randomized, open-label, phase 2 study enrolled treatment-naive, noncirrhotic patients with HCV genotype 1a. Patients were randomized 1:1 into Arms A and B, and then enrolled in Arm C. Patients received ombitasvir/paritaprevir/ritonavir plus dasabuvir for 12 weeks with either: no RBV for the first 2 weeks followed by weight-based dosing thereafter (Arm A), weight-based RBV for all 12 weeks (Arm B), or low-dose RBV (600 mg) once daily for all 12 weeks. Fine needle aspiration (FNA) was used to determine HCV RNA decline within liver.Results: Baseline HCV RNA was higher and declined more rapidly in plasma than liver; however, RBV dosing did not impact either median plasma or liver HCV RNA decline during the first 2 weeks of treatment. Liver-to-plasma drug concentrations were variable over time. The most common adverse event was pain associated with FNA.Conclusions: Coadministration of RBV had minimal visible impact on the plasma or liver kinetics of HCV RNA decline during the first 2 weeks of treatment, regardless of RBV dosing. [ABSTRACT FROM AUTHOR]