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Arzneimittelforschung 2010; 60(10): 636-639
DOI: 10.1055/s-0031-1296338
Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Influence of pre-analytical conditions on plasma ribavirin concentrations

Peggy Gandia
1   Laboratoire de Pharmacocinétique et Toxicologic Clinique, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
,
Stéphanie Trancart
1   Laboratoire de Pharmacocinétique et Toxicologic Clinique, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
,
Florence Nicot
2   Laboratoire de Virologie, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
,
Karl Barange
3   Service de Gastro-Entérologie, Hôpital Purpan, Toulouse, (France)
,
Laurent Alric
4   Service de Médecine Interne, Hôpital Purpan, Toulouse, (France)
,
Jacques Izopet
2   Laboratoire de Virologie, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
,
Patrick Séraissol
1   Laboratoire de Pharmacocinétique et Toxicologic Clinique, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
,
Michel Lavit
1   Laboratoire de Pharmacocinétique et Toxicologic Clinique, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
,
Georges Houin
1   Laboratoire de Pharmacocinétique et Toxicologic Clinique, Institut Fédératif de Biologie, Hôpital Purpan, Toulouse, (France)
› Author Affiliations
Further Information

Publication History

Publication Date:
03 December 2011 (online)

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Abstract

Ribavirin (CAS 66510-90-5) associated to peginterferon (CAS 99210-65-8) is the current Standard treatment for chronic hepatitis C. Exposure to ribavirin influences the virological response and anemia. Therefore monitoring plasma concentration of ribavirin is a useful tool for individualizing ribavirin dosing regimens. Ribavirin is a substrate of several nucleoside transporters that play a role in its distribution in erythrocytes. After blood sampling, it is essential to limit this mechanism. The aim of this study was to evaluate the influence of temperature and time on ribavirin plasma concentrations.

Two blood samples, collected in EDTA tubes, were taken at the same time from 23 patients. One sample was conserved on ice whereas the second one was kept at room temperature during transport to the laboratory. Upon receipt at the laboratory and at different times post-reception (from 1 to 3 h), 1.5 mL of blood from each sample was centrifuged to obtain plasma that was then stored at −20 °C until assay. Samples were maintained in the same conditions as during transport for the 3 h. Plasma ribavirin was analysed using an HPLC-UV system.

The results showed that mean loss of ribavirin concentration, for samples kept on ice as well as at room temperature, was less than 3%, 9% and 13% after 1, 2 and 3 h, respectively. These results suggest that blood samples for ribavirin analysis can be sent at room temperature within a period of 2 h between sampling and centrifugation.

Key words

Antiviral drugs - CAS 66510-90-5 - High-performance liquid chromatography - Ribavirin - Therapeutic drug monitoring
 

  • References

  • 1 Feld JJ, Hoofnagle JH. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature. 2005; 436: 967-72
    CrossrefPubMedGoogle Scholar
  • 2 Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001; 358: 958-65
    CrossrefPubMedGoogle Scholar
  • 3 Fried MW, Shiftman ML, Reddy KR, Smith C, Marinos G, Goncales Jr. FL et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347: 975-82
    CrossrefPubMedGoogle Scholar
  • 4 Hadziyannis SI, Sette Jr H, Morgan TR, Balan V, Diago M, Marcellin P et al. Peginterferon-alpha 2a and ribavirin combination therapy in chronic Hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004; 140: 346-55
    CrossrefPubMedGoogle Scholar
  • 5 Larrat S, Stanke-Labesque F, Plages A, Zarski IP, Bessard G, Souvignet C. Ribavirin quantification in combination treatment of chronic hepatitis C. Antimicrob Agents Chemother. 2003; 47: 124-9
    CrossrefPubMedGoogle Scholar
  • 6 Nicot F, Legrand-Abravanel F, Lafont T, Dubois M, Saune K, Pasquier C et al. Serum concentrations of ribavirin and pegylated interferon and viral responses in patients infected with HIV and HCV. J Med Virol. 2008; 80: 1523-9
    CrossrefPubMedGoogle Scholar
  • 7 Back D, Gatti G, Fletcher C, Garaffo R, Haubrich R, Hoetelmans R et al. Therapeutic drug monitoring in HIV infection: current status and future directions. AIDS. 2002; 16 (01) S5-37
    CrossrefPubMedGoogle Scholar
  • 8 Ribera E, Lopez-Cortes LF, Soriano V, Casado JL, Mallolas J. Therapeutic drug monitoring and the inhibitory quotient of antiretroviral drugs: can they be applied to the current situation?. Enferm Infecc Microbiol Clin. 2005; 23: 55-67
    CrossrefPubMedGoogle Scholar
  • 9 Maynard M, Pradat P, Gagnieu MC, Souvignet C, Trepo C. Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients. Antivir Ther. 2008; 13: 607-11
    PubMedGoogle Scholar
  • 10 Morello J, Rodriguez-Novoa S, Jimenez-Nacher I, Soriano V. Usefulness of monitoring ribavirin plasma concentrations to improve treatment response in patients with chronic hepatitis C. J Antimicrob Chemother. 2008; 62: 1174-80
    CrossrefPubMedGoogle Scholar
  • 11 Rendon AL, Nunez M, Romero M, Barreiro P, Martin-Carbonero L, Garcia-Samaniego J et al. Early monitoring of ribavirin plasma concentrations may predict anemia and early virologic response in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Deflc Syndr. 2005; 39: 401-5
    PubMedGoogle Scholar
  • 12 Loustaud-Ratti V, Stanke-Labesque F, Marquet P, Gagnieu MC, Maynard M, Babany G et al. Optimizing ribavirin dosage: a new challenge to improve treatment efficacy in genotype 1 hepatitis C patients. Gastroenterol Clin Biol. 2009; 33: 580-3
    CrossrefPubMedGoogle Scholar
  • 13 Maeda Y, Kiribayashi Y, Moriya T, Maruhashi A, Omoda K, Funakoshi S et al. Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C. Ther Drug Monit. 2004; 26: 9-15
    CrossrefPubMedGoogle Scholar
  • 14 Lindahl K, Stahle L, Bruchfeld A, Schvarcz R. High-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C. Hepatology. 2005; 41: 275-9
    CrossrefPubMedGoogle Scholar
  • 15 larvis SM, Thorn IA, Glue P. Ribavirin uptake by human erythrocytes and the involvement of nitrobenzylthioinosinesensitive (es)-nucleoside transporters. Br J Pharmacol. 1998; 123: 1587-92
    CrossrefPubMedGoogle Scholar
  • 16 Melendez M, Rosario O, Zayas B Rodriguez IF. HPLCMS/MS method for the intracellular determination of ribavirin monophosphate and ribavirin triphosphate in CEM ss cells. J Pharm Biomed Anal. 2009; 49: 1233-40
    CrossrefPubMedGoogle Scholar
  • 17 Granich GG, Krogstad DJ, Connor JD, Desrochers KL, Sherwood C. High-performance liquid chromatography (HPLC) assay for ribavirin and comparison of the HPLC assay with radioimmunoassay. Antimicrob Agents Chemother. 1989; 33: 311-5
    CrossrefPubMedGoogle Scholar
  • 18 FDA Guidance for Industry — Bioanalytical Method Validation; 2001.
    PubMed
  • 19 Marquet P, Sauvage FL, Loustaud-Ratti V, Babany G, Rousseau A, Lachatre G. Stability of ribavirin concentrations depending on the type of blood collection tube and pre-analytical conditions. Ther Drug Monit. 2010; 32 (2) 237-41
    PubMedGoogle Scholar
  • 20 Loregian A, Scarpa MC, Pagni S, Parisi SG, Palu G. Measurement of ribavirin and evaluation of its stability in human plasma by high-performance liquid chromatography with UV detection. J Chromatogr B. 2007; 856: 358-64
    CrossrefPubMedGoogle Scholar