I am aware that high fat intake w/riba increases bioavailability, ANY other ideas???
Adequate Ribavirin exposure after the first dose predicts SVR in genotype 1 patients
7th July 2008 By Liz Highleyman hivandhepatitis.com
Studies continue to show that adequate doses of ribavirin, which helps to prevent relapse after completion of therapy, are important for optimal treatment of chronic hepatitis C virus (HCV) infection.
Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs and health care workers or emergency workers who may be exposed to contaminated blood.
But actual ribavirin concentrations achieved in the body after dosing may be more relevant than the amount administered, according to a French study published in the May 2008 issue of Hepatology.
As background, the authors noted that previous studies showed "marked inter-individual variability" of ribavirin concentrations despite dose adjustment based on body weight. Furthermore, data suggested that there was a correlation between single time point ribavirin concentrations and achievement of sustained virological response (SVR), or continued undetectable HCV viral load 24 weeks after completion of treatment. None of these studies, however, evaluated global exposure to ribavirin.
In the present study, the investigators conducted an exploratory pharmacokinetic-pharmacodynamic analysis of 28 genotype 1 chronic hepatitis C patients treated with pegylated interferon alfa-2a (Pegasys) plus weight-based ribavirin for 12 weeks, with amantadine (an influenza drug once studied as an experimental anti-HCV therapy) added for an additional 36 weeks; 24 participants completed the study.
Full and abbreviated ribavirin area under the concentration time curve from 0 to 4 and 0 to 12 hours (AUC(0-4h), AUC(0-12h)) were derived from plasma concentration profiles at day 0, week 12, week 12 + 1 day, and week 24. Virological response was assessed at day 0 (0, 12, and 24 hours), at weeks 2, 4, and 6, and then monthly through week 72, using a TaqMan polymerase chain reaction assay with an HCV viral load threshold of 15 IU/mL.
• Patients who achieved SVR had a significantly higher ribavirin concentrations at day 0:
- AUC(0-4h): 2010 vs 1340 microg/hour/L (P = 0.03).
- AUC(0-12h): 3695 vs 2937 microg/hour/L (P = 0.03);
• Patients with day 0 AUCs above the cut-off values defined by receiver operating characteristic curves (1755 microg/hour/L for AUC(0-4h) and 3014 microg/hour/L for AUC(0-12h)) had a significantly better chance of achieving SVR than participants with AUCs under these thresholds (odds ratio 16.0 and 8.9, respectively; both P = 0.02).
"Ribavirin exposure at [day 0] is significantly related to SVR," the study authors concluded. "We propose a minimum AUC(0-4h) threshold of 1755 microg/hour/L at [day 0] as a target for ribavirin dose adjustment."
"To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR," they added.
If these findings are confirmed, early ribavirin concentration may be added to the several other factors (including HCV genotype, pre-treatment viral load, and rapid virological response) that can be used to predict - and ideally improve -- the chances of sustained response to hepatitis C treatment.
V Loustaud-Ratti, S Alain, A Rousseau, and others. Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C. Hepatology 47(5):1453-1461. May 2008. Abstract