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. 2012 Apr 12;2(1):42–54. doi: 10.1016/S0973-6883(12)60090-5

A Pharmacological Profile of Ribavirin and Monitoring of its Plasma Concentration in Chronic Hepatitis C Infection

Girish S Naik 1, Manoj G Tyagi 1,*
PMCID: PMC3940409  PMID: 25755405

Abstract

Chronic hepatitis C (CHC) infection, usually an asymptomatic infection, has long-term serious complications such as cirrhosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation (LT). Several novel drugs against hepatitis C which form part of ‘specifically targeted antiviral therapy for hepatitis C’ (STAT-C) have been developed. These include NS3/4A protease inhibitors telaprevir, boceprevir, and nucleoside/non-nucleoside polymerase inhibitors (NS5A) which hold promise for future therapy. Despite the development of new anti-hepatitis C virus (HCV) drugs, ribavirin (RBV) remains the single most important drug to prevent relapse and is frequently included among newer regimens being developed with novel small molecule anti-HCV drugs. The current approved treatment is a combination therapy of once weekly subcutaneous pegylated-interferon (PEG-IFN)-α plus body-weight-based oral RBV regimen. The most significant dose-dependent side effect of RBV is hemolytic anemia warranting dose reduction or discontinuation in severe cases compromising sustained virological response (SVR). Monitoring RBV plasma concentration has been challenging due to its peculiar pharmacokinetics and has been done to predict both efficacy and toxicity. Herein, we review the pharmacological profile of RBV and the monitoring of its plasma concentration, monitoring in renal impairment, post-LT, and human immunodeficiency virus (HIV)-HCV co-infection in patients being treated with combination therapy of PEG-IFN-α and RBV.

Keywords: HCV, plasma concentration, ribavirin, TDM

Abbreviations: ADSS, adenylosuccinate synthetase; ATP, adenosine-5′-triphosphate; AUC, area under concentration curve; BMD, bone mineral density; Css, concentration at steady-state; Ctrough, trough concentration; DAAs, directly acting antiviral agents; EPO, erythropoietin; EVR, early virological response; FDA, Food and Drug Administration; GTP, guanosine-5′-triphosphate; Hb, hemoglobin; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HPLC, high-performance liquid chromatography; IFN, interferon; IMPDH, inosine-5′-monophosphate dehydrogenase; ITPA, inosine triphosphate pyro-phosphatase; PEG-IFN, pegylated-interferon; PSH, protein sulfhydryl; RBC, red blood cell; RBV, ribavirin; RNA, ribonucleic acid; RSV, respiratory syncytial virus; RVR, rapid virological response; STAT-C, specifically targeted therapy for hepatitis C; SVR, sustained virological response; TDM, therapeutic drug monitoring

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