Ribavirin in combination with pegylated interferon alpha is the current standard treatment for chronic hepatitis C. Adequate exposure to ribavirin seems crucial for achieving the best virological response. However, anaemia is a frequent, dose-dependent limiting side effect of ribavirin use. Therefore, therapeutic drug monitoring of ribavirin plasma concentrations could be a useful tool for indi...

We investigated the relationship between serum ribavirin concentrations and clearance, as well as therapeutic efficacy and adverse reactions, in 97 Japanese patients with chronic hepatitis C virus infections treated with a 6-month course of high-dose alpha2b interferon (6 million units/day) plus ribavirin (600 to 800 mg/day) combination therapy. This randomized trial showed that the saturation ...

To enhance the inhibitory potential of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) vs hepatitis C virus (HCV) NTPase/helicase, ribavirin-5'-triphosphate (ribavirin-TP) was synthesized and investigated. Ribavirin-TP was prepared with the use of modified Yoshikawa-Ludwig-Mishra-Broom procedure (cf. Mishra & Broom, 1991, J. Chem. Soc., Chem. Commun, 1276-1277) involving phospho...

BACKGROUND Paramyxovirus (PV) infections are increasingly recognized in lung transplant recipients and have been linked to subsequent graft failure and bronchiolitis obliterans syndrome (BOS). Ribavirin represents a possible treatment option although the outcome on graft function and BOS incidence is unknown. METHODS We analysed outcomes of all PV infections in lung/heart-lung recipients betw...

The polar nucleoside drug ribavirin is front-line treatment for chronic hepatitis C virus infection. The human equilibrative nucleoside transporter (ENT) 1 transports ribavirin into erythrocytes where it is phosphorylated. These phosphorylated metabolites accumulate in the erythrocytes and produce dose-limiting hemolytic anemia. Here, we examined the in vitro and ex vivo transport and metabolis...

Chronic hepatitis C infection is a global health problem with 170 million patients infected. Hepatitis C virus (HCV) infection is a leading cause of end stage liver disease. Current antiviral treatment options available are not optimal either regarding cure of disease or risk of side effects. The aim of the studies in this thesis was to investigate the pharmacokinetic-pharmacodynamic relationsh...

The effects of intracellular ribavirin on morphology and redistribution of phosphatidylserine (PS) in human erythrocytes were examined. Erythrocytes were incubated with 1 mM ribavirin in the presence/absence of dipyridamole, an inhibitor of es-type nucleoside transporter. Intracellular ribavirin was accumulated in erythrocytes with the concentration of 1361 muM, which corresponds to the blood l...

The current standard of care for hepatitis C virus (HCV) infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only ∼50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation...

Ribavirin in combination with alpha 2 interferon is the consensus treatment for chronic hepatitis C. However, recent preliminary pharmacological studies have suggested that the bioavailability of ribavirin displays great interindividual variability. In order to monitor serum ribavirin levels during combination treatment, we developed and validated a quantitative assay using an approach adaptabl...