This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Larrat, S.
Right arrow Articles by Souvignet, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Larrat, S.
Right arrow Articles by Souvignet, C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2003, p. 124-129, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.124-129.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Ribavirin Quantification in Combination Treatment of Chronic Hepatitis C

Sylvie Larrat,1 Françoise Stanke-Labesque,1* Agnès Plages,2 Jean-Pierre Zarski,2 Germain Bessard,1 and Claude Souvignet2

Laboratory of Pharmacology,1 Hepato-Gastro-Enterology Department, Grenoble University Hospital, BP217, F-38043 Grenoble Cedex 09, France2

Received 29 May 2002/ Returned for modification 13 August 2002/ Accepted 7 October 2002

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 adaptable for routine hospital laboratories. The method involved solid-phase extraction on phenyl boronic acid cartridges followed by high-performance liquid chromatography with a C18-bonded silica column and a mobile phase containing 10 mM ammonium phosphate buffer (with the pH adjusted to 2.5) and UV detection (207 nm). The sensitivity, recovery, linearity of the calibration curve, intra- and interassay accuracies, precision, and stability at 4°C were consistent with its use in the laboratory routine. In addition, other nucleoside analogues sometimes used with ribavirin in patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus did not interfere with the quantification of ribavirin levels. The ribavirin concentration was quantified in 24 serum samples from patients with chronic hepatitis C treated with a combination of ribavirin and alpha 2 interferon. The mean serum ribavirin concentration was 2.67 ± 1.06 µg/ml (n = 24) at week 12 of treatment (W12) and 3.24 ± 1.35 µg/ml (n = 24) at week 24 of treatment (W24). In addition, ribavirin concentrations displayed high interindividual variabilities: the coefficients of variation of the serum ribavirin concentrations adjusted to the administered dose were 44 and 48% at W12 and W24, respectively. Moreover, the ribavirin concentration was higher in patients with a sustained virological response (n = 11) than in patients with treatment failure (n = 13), with significant intergroup differences at W12 (P = 0.030) and W24 (P = 0.049). The present study describes a simple analytical method for the quantification of ribavirin in human serum that could be a useful tool for the monitoring of ribavirin concentrations in HCV-infected patients in order to improve the efficacy and safety of therapy with ribavirin plus interferon.

* Corresponding author. Mailing address: Laboratory of Pharmacology, Albert Michallon Hospital, BP217, 38043 Grenoble Cedex 09, France. Phone: 33 (0)4 76 76 54 92. Fax: 33 (0)4 76 75 89 38. E-mail: FStanke{at}chu-grenoble.fr.

Antimicrobial Agents and Chemotherapy, January 2003, p. 124-129, Vol. 47, No. 1
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.1.124-129.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ibarra, K. D., Pfeiffer, J. K. (2009). Reduced Ribavirin Antiviral Efficacy via Nucleoside Transporter-Mediated Drug Resistance. J. Virol. 83: 4538-4547 [Abstract] [Full Text]  
  • Morello, J., Rodriguez-Novoa, S., Jimenez-Nacher, I., Soriano, V. (2008). Usefulness of monitoring ribavirin plasma concentrations to improve treatment response in patients with chronic hepatitis C. J Antimicrob Chemother 62: 1174-1180 [Abstract] [Full Text]  
  • Aguilar Marucco, D., Gonzalez de Requena, D., Bonora, S., Tettoni, C., Bonasso, M., De Blasi, T., D'Avolio, A., Sciandra, M., Siccardi, M., Baietto, L., Trentini, L., Sinicco, A., Cariti, G., Di Perri, G. (2008). The use of trough ribavirin concentration to predict sustained virological response and haematological toxicity in HIV/HCV-co-infected patients treated with ribavirin and pegylated interferon. J Antimicrob Chemother 61: 919-924 [Abstract] [Full Text]  
  • Saito, H., Tada, S., Ebinuma, H., Ishii, H., Kashiwazaki, K., Takahashi, M., Tsukada, N., Nishida, J., Tanaka, S., Shiozaki, H., Hibi, T. (2006). Role of erythrocytes as a reservoir for ribavirin and relationship with adverse reactions in the early phase of interferon combination therapy for chronic hepatitis C virus infections.. J. Clin. Microbiol. 44: 3562-3568 [Abstract] [Full Text]  
  • Boulestin, A., Kamar, N., Legrand-Abravanel, F., Sandres-Saune, K., Alric, L., Vinel, J.-P., Rostaing, L., Izopet, J. (2004). Convenient Biological Assay for Polyethylene Glycol-Interferons in Patients with Hepatitis C. Antimicrob. Agents Chemother. 48: 3610-3612 [Abstract] [Full Text]  
  • Buckwold, V. E. (2004). Implications of finding synergic in vitro drug-drug interactions between interferon-{alpha} and ribavirin for the treatment of hepatitis C virus. J Antimicrob Chemother 53: 413-414 [Abstract] [Full Text]  
  • Bruchfeld, A., Lindahl, K., Stahle, L., Soderberg, M., Schvarcz, R. (2003). Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant 18: 1573-1580 [Abstract] [Full Text]  
  • Bruchfeld, A., Lindahl, K., Stahle, L., Soderberg, M., Schvarcz, R. (2003). Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant 18: 1573-1580 [Abstract] [Full Text]  
  • Buckwold, V. E., Wei, J., Wenzel-Mathers, M., Russell, J. (2003). Synergistic In Vitro Interactions between Alpha Interferon and Ribavirin against Bovine Viral Diarrhea Virus and Yellow Fever Virus as Surrogate Models of Hepatitis C Virus Replication. Antimicrob. Agents Chemother. 47: 2293-2298 [Abstract] [Full Text]  
  • Pfeiffer, J. K., Kirkegaard, K. (2003). A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity. Proc. Natl. Acad. Sci. USA 100: 7289-7294 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»