title: Ribavirin levels in post liver transplant patients treated for recurrent hepatitis C viral infection.
abstract: Hepatitis C virus (HCV) infection is the most common indication for liver transplantation (LTx) in the United States. Ribavirin with pegylated interferon is the only treatment option for HCV recurrence in post-LTx patients. In clinical practice, for more than 50% of patients, ribavirin dose needs to be modified.
  
  
  OBJECTIVE
  The aim of this study was to examine the role of ribavirin level and its relevance in the management of post-LTx patients in terms of renal dysfunction, efficacy, toxicity, and potential drug interactions.
  
  
  METHODS
  Thirty-four blood samples were available from 22 post-LTx patients. Ribavirin concentrations in plasma (all samples) and whole blood concentrations (16 samples) were examined. The dose of ribavirin ranged from 400 mg/d to 1000 mg/d, but concentrations were normalized to 800 mg/d.
  
  
  RESULTS
  There was a wide variation in plasma concentration of ribavirin, ranging from 1.8 to 122.1 mg/mL. The concentrations were similar in whole blood and plasma. Dose-normalized concentration with creatinine clearance below 70 mL/min were significantly higher when compared with creatinine clearance above 70 mL/min (P = .015). Eleven patients required erythropoietin; their mean ribavirin dosage was higher but mean ribavirin concentration was lower compared to the 11 patients who did not require erythropoietin factor. There was no difference in mean ribavirin concentration in patients who cleared the virus (n = 7) compared and who did not clear the virus (n = 9). Three patients were on nucleoside reverse transcriptase inhibitors (NRTI) had significantly higher concentration (mean 87.1 microg/mL) compared to those who did not receive NRTI (mean 34.4 microg/mL, P = .00)
  
  
  CONCLUSIONS
  Ribavirin concentration in plasma and whole blood were similar, with a wide variation. Patients with impaired renal function and those who were on NRTI had significantly higher concentrations of ribavirin. The ribavirin concentrations did not predict either the clearance of HCV RNA or the need for erythropoitin factor.
authors.affiliation: Strong Memorial Hospital, Department of Surgery, Transplant Division, University of Rochester, Rochester, New York 14642, USA. Ashok_jain@urmc.Rochester.edu
authors.forename: A
authors.initials: A
authors.lastname: Jain
authors.forename: R
authors.initials: R
authors.lastname: Vekatramanan
authors.forename: B
authors.initials: B
authors.lastname: Yelochan
authors.forename: R
authors.initials: R
authors.lastname: Kashyap
authors.forename: A
authors.initials: A
authors.lastname: Marcos
authors.forename: J
authors.initials: J
authors.lastname: Fung
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000627:therapeutic use; D006526:Hepatitis C / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D012254:Ribavirin; D000068817:Epoetin Alfa