title: Ribavirin levels and haemoglobin decline in early virological responders and non-responders to hepatitis C virus combination therapy.
abstract: Therapeutic drug monitoring of ribavirin has been claimed to predict virological response and/or haematological side effects in patients with chronic hepatitis C undergoing peginterferon/ribavirin combination treatment. In the present study, steady-state ribavirin levels were retrospectively analyzed in serum samples from patients at week 12 of combination therapy with peginterferon alpha-2a or alpha-2b and ribavirin. Patients were classified as early virological responders on the basis of undetectable HCV-RNA or HCV-RNA drop >or=2 log from baseline at week 12. The mean ribavirin level was not different between early virological responders (2.3 +/- 0.1 microg/ml, n = 45) and early virological non-responders (2.0 +/- 0.2 microg/ml, n = 10). There was no correlation between ribavirin levels at week 12 and early virological response. In patients with early virological response, haemoglobin (Hb) levels were found to be decreased by 18% on average from the basal values; however, in only 2 patients Hb levels declined below 100 g/l. There was a moderate negative correlation between ribavirin levels and Hb levels at week 12 (R = -0.50, p < 0.001); however, ribavirin levels did not correlate with relative or absolute decline in Hb as compared to basal levels or with ribavirin dose per kilogram body weight. In addition, a significant negative correlation between ribavirin levels and glomerular filtration rate was found (R = -0.31, p < 0.05). Based on our results, monitoring of ribavirin serum levels at week 12 of HCV combination therapy does not appear to predict early virological response or reductions in Hb levels. Further research is needed to assess their diagnostic value at other time points of peginterferon/ribavirin combination treatment and/or in patients with renal insufficiency.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University Graz, Graz, Austria. josef.donnerer@meduni-graz.at
authors.forename: Josef
authors.initials: J
authors.lastname: Donnerer
authors.forename: Maja
authors.initials: M
authors.lastname: Grahovac
authors.forename: Evelyn
authors.initials: E
authors.lastname: Stelzl
authors.forename: Harald H
authors.initials: HH
authors.lastname: Kessler
authors.forename: Csilla
authors.initials: C
authors.lastname: Bankuti
authors.forename: Vanessa
authors.initials: V
authors.lastname: Stadlbauer
authors.forename: Rudolf E
authors.initials: RE
authors.lastname: Stauber
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use*; D001793:Blood Preservation / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018450:Disease Progression; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006207:Half-Life; D006454:Hemoglobins / Q000032:analysis*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a