Abstract
Purpose
This study describes the pharmacokinetics, safety, and tolerability of ribavirin in hemodialysis-dependent patients.
Methods
Six adult patients (4 male, 2 female) were recruited from a hemodialysis clinic where they were receiving regular hemodialysis sessions. Patients received a single oral 400-mg dose of ribavirin (2 × 200-mg capsules) after an overnight fast. A 4-h hemodialysis session was performed between 6 and 10 h post-dose. Plasma and urinary concentrations of ribavirin were determined using validated high-performance liquid chromatography/tandem mass spectrometric methods.
Results
Single oral doses of ribavirin 400 mg were safe and well tolerated in this population. Urinary excretion of ribavirin over 48 h was minimal (0.6 mg: approximately 0.14% of the dose). The mean amount removed during the 4-h hemodialysis session (9.6 mg) represented approximately 2.4% of the dose.
Conclusions
Ribavirin hemodialysis clearance (CLhd = 74.5 ml/min) represented approximately 50% of the renal clearance (CLr) measured in subjects with normal renal function (CLr = 129 ml/min).
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References
Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK (1972) Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science 177:705–706
Martin P, Jensen DM (2008) Ribavirin in the treatment of chronic hepatitis C. J Gastroenterol Hepatol 23:844–855
Glue P (1999) The clinical pharmacology of ribavirin. Semin Liver Dis 19 [Suppl 1]:17–24
Glue P, Tan Y, Sack M, Schencker S, Zambas D, Gupta SK (1999) Use of ribavirin in special populations—pharmacokinetic data and biological relevance. Hepatology 30:309A
Glue P, Schenker S, Gupta S, Clement RP, Zambas D, Salfi M (2000) The single dose pharmacokinetics of ribavirin in subjects with chronic liver disease. Br J Clin Pharmacol 49:417–421
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Dekker, New York, pp 409–417
Data on File. Merck Research Laboratory, Kenilworth, NJ
Kramer TH, Gaar GG, Ray CG, Minnich L, Copeland JG, Connor JD (1990) Hemodialysis clearance of intravenously administered ribavirin. Antimicrob Agents Chemother 34:489–490
Singlas E, Taburet F, Lebas B, De Curzon OP, Sobel A, Chauveau P, Viron B, Khayat RA, Poignet JL, Mignon F, Humbert G, Fillastre JP (1992) Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis. Antimicrob Agents Chemother 36:1519–1524
Singlas E, Pioger JC, Taburet AM, Colin JN, Fillastre JP (1989) Zidovudine disposition in patients with severe renal impairment: influence of hemodialysis. Clin Pharmacol Ther 46:190–197
Copegus™ prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021511s023lbl.pdf. Accessed 14 September 11
Tan ACTTL, Brouwer JT, Glue P, van Leusen R, Kauffmann RH, Schalm SW, de Vries RA, Vroom B (2001) Safety of interferon and ribavirin therapy in hemodialysis patients with chronic hepatitis C: results of a pilot study. Nephrol Dial Transplant 16:193–195
Bruchfeld A, Stahle L, Andersson J, Schvarcz R (2001) Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection—a pilot study. J Viral Hepat 8:287–292
Van Leusen R, Adang RP, de Vries RA, Cnossen TT, Konings CJ (2008) Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with chronic hepatitis C. Nephrol Dial Transplant 23:721–725
Rendina M, Schena A, Castellaneta NM, Losito F, Amoruso AC, Stallone G, Schena FP, Di Leo A, Francavilla A (2007) The treatment of chronic hepatitis C with peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed patients awaiting renal transplant. J Hepatol 46:768–774
Acknowledgements
Authors appreciate the following for their support of this research: Dr. Marshall Sack of Radiant Research for recruiting and testing patients.
Financial disclosure
This study was funded by Merck & Co, Inc.; Whitehouse Station, NJ, USA. All authors were employees of Schering-Plough Research Institute at the time when this research was performed.
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Gupta, S.K., Kantesaria, B. & Glue, P. Pharmacokinetics, safety, and tolerability of ribavirin in hemodialysis-dependent patients. Eur J Clin Pharmacol 68, 415–418 (2012). https://doi.org/10.1007/s00228-011-1137-x
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DOI: https://doi.org/10.1007/s00228-011-1137-x