Skip to main content
SpringerLink
Log in
Book cover

Chagas Disease pp 299–312Cite as

Clinical Pharmacology of Drugs for the Treatment of Chagas Disease

  • Chapter
  • First Online:

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

Chagas disease is a parasitic disease endemic to Latin America that, if left untreated, can lead to severe long-term organ damage, particularly in the heart and gastrointestinal tract. Treatment with benznidazole or nifurtimox has been shown to be effective in the acute phase and during childhood, and limited evidence suggest a beneficial effect later in life too. However, both drugs require prolonged treatments (30–60 days) and are associated to significant adverse events that increase in severity and prevalence with age. Prompt pediatric diagnosis and treatment are vital for an effective use of these medications.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010;375(9723):1388–402. PubMed PMID: 20399979.

    Article  PubMed  Google Scholar 

  2. Schmunis GA. Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Mem Inst Oswaldo Cruz. 2007;102(Suppl 1):75–85. PubMed PMID: 17891282.

    Article  PubMed  Google Scholar 

  3. Schmunis GA, Yadon ZE. Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop. 2010;115(1–2):14–21. PubMed PMID: 19932071.

    Article  PubMed  Google Scholar 

  4. Carlier Y. Globalization of Chagas disease (American trypanosomiasis): the situation in Europe and Belgium. Bull Mem l’Acad R Med Belg. 2011;166(10–12):347–55. discussion 56–7. PubMed PMID: 23082500.

    CAS  Google Scholar 

  5. Teixeira AR, Nitz N, Guimaro MC, Gomes C, Santos-Buch CA. Chagas disease. Postgrad Med J. 2006;82(974):788–98. Pubmed Central PMCID: 2653922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Teixeira AR, Nascimento RJ, Sturm NR. Evolution and pathology in Chagas disease—a review. Mem Inst Oswaldo Cruz. 2006;101(5):463–91. PubMed PMID: 17072450.

    Article  PubMed  Google Scholar 

  7. Apt W. Current and developing therapeutic agents in the treatment of Chagas disease. Drug Des Devel Ther. 2010;4:243–53. PubMed PMID: 20957215. Pubmed Central PMCID: 2948934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stoppani AOM. Quimioterapia de la enfermedad de Chagas. Medicina (B Aires). 1999;59(Suppl 2):147–65.

    Google Scholar 

  9. Buckner FS, Bahia MT, Suryadevara PK, White KL, Shackleford DM, Chennamaneni NK, et al. Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib. Antimicrob Agents Chemother. 2012;56(9):4914–21. PubMed PMID: 22777048. Pubmed Central PMCID: 3421879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chatelain E. Chagas disease drug discovery: toward a new era. J Biomol Screen. 2015;20(1):22–35. PubMed PMID: 25245987.

    Article  PubMed  CAS  Google Scholar 

  11. Molina I, Gomez i, Prat J, Salvador F, Trevino B, Sulleiro E, Serre N, et al. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med. 2014;370(20):1899–908. PubMed PMID: 24827034.

    Article  PubMed  CAS  Google Scholar 

  12. Perez-Molina JA, Molina I. Chagas disease. Lancet. 2018;391(10115):82–94. PubMed PMID: 28673423.

    Article  PubMed  Google Scholar 

  13. Sales Junior PA, Molina I, Fonseca Murta SM, Sanchez-Montalva A, Salvador F, Correa-Oliveira R, et al. Experimental and clinical treatment of Chagas disease: a review. Am J Trop Med Hyg. 2017;97(5):1289–303. PubMed PMID: 29016289.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Wilkinson SR, Bot C, Kelly JM, Hall BS. Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives. Curr Top Med Chem. 2011;11(16):2072–84. PubMed PMID: 21619510.

    Article  CAS  PubMed  Google Scholar 

  15. Hall BS, Bot C, Wilkinson SR. Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites. J Biol Chem. 2011;286(15):13088–95. Pubmed Central PMCID: 3075655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wilkinson SR, Taylor MC, Horn D, Kelly JM, Cheeseman I. A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc Natl Acad Sci U S A. 2008;105(13):5022–7. PubMed PMID: 18367671. Pubmed Central PMCID: 2278226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Vazquez K, Paulino M, Salas CO, Zarate-Ramos JJ, Vera B, Rivera G. Trypanothione reductase: a target for the development of anti-Trypanosoma cruzi drugs. Mini Rev Med Chem. 2017;17(11):939–46. PubMed PMID: 28302040.

    Article  CAS  PubMed  Google Scholar 

  18. Paulino M, Iribarne F, Dubin M, Aguilera-Morales S, Tapia O, Stoppani AO. The chemotherapy of Chagas’ disease: an overview. Mini Rev Med Chem. 2005;5(5):499–519. PubMed PMID: 15892691.

    Article  CAS  PubMed  Google Scholar 

  19. de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet. 1996;348(9039):1407–13. PubMed PMID: 8937280.

    Article  PubMed  Google Scholar 

  20. Viotti R, Alarcon de Noya B, Araujo-Jorge T, Grijalva MJ, Guhl F, Lopez MC, et al. Towards a paradigm shift in the treatment of chronic Chagas disease. Antimicrob Agents Chemother. 2014;58(2):635–9. PubMed PMID: 24247135. Pubmed Central PMCID: 3910900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Viotti R, Vigliano C, Lococo B, Alvarez MG, Petti M, Bertocchi G, et al. Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities. Expert Rev Anti-Infect Ther. 2009;7(2):157–63. PubMed PMID: 19254164.

    Article  CAS  PubMed  Google Scholar 

  22. Sosa Estani S, Segura EL, Ruiz AM, Velazquez E, Porcel BM, Yampotis C. Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas’ disease. Am J Trop Med Hygiene. 1998;59(4):526–9. PubMed PMID: 9790423.

    Article  CAS  Google Scholar 

  23. Altcheh J, Moscatelli G, Moroni S, Garcia-Bournissen F, Freilij H. Adverse events after the use of benznidazole in infants and children with Chagas disease. Pediatrics. 2011;127(1):e212–8. PubMed PMID: 21173000.

    Article  PubMed  Google Scholar 

  24. Marin-Neto JA, Rassi Júnior A, Mattos AC, Avezum Júnior A, Rassi A. The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease. Mem Inst Oswaldo Cruz. 2009;104(Suppl 1):319–24.

    Article  CAS  PubMed  Google Scholar 

  25. Fernández ML, Marson ME, Ramirez JC, Mastrantonio G, Schijman AG, Altcheh J, et al. Pharmacokinetic and pharmacodynamic responses in adult patients with Chagas disease treated with a new formulation of benznidazole. Mem Inst Oswaldo Cruz. 2016;111(3):218–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Garcia-Bournissen F, Moroni S, Marson ME, Moscatelli G, Mastrantonio G, Bisio M, et al. Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease. Arch Dis Child. 2015;100(1):90–4. PubMed PMID: 25210104.

    Article  PubMed  Google Scholar 

  27. Altcheh J, Moscatelli G, Mastrantonio G, Moroni S, Giglio N, Marson ME, et al. Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults. PLoS Negl Trop Dis. 2014;8(5):e2907. PubMed PMID: 24853169. Pubmed Central PMCID: 4031103.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Garcia-Bournissen F, Altcheh J, Giglio N, Mastrantonio G, Della Vedova CO, Koren G. Pediatric clinical pharmacology studies in Chagas disease: focus on Argentina. Paediatr Drugs. 2009;11(1):33–7. PubMed PMID: 19127950.

    Article  PubMed  Google Scholar 

  29. Jannin J, Villa L. An overview of Chagas disease treatment. Mem Inst Oswaldo Cruz. 2007;102(Suppl 1):95–7. PubMed PMID: 17906803.

    Article  PubMed  Google Scholar 

  30. Pinheiro E, Brum-Soares L, Reis R, Cubides J-C. Chagas disease: review of needs, neglect, and obstacles to treatment access in Latin America. Rev Soc Bras Med Trop. 2017;50(3):296–300.

    Article  PubMed  Google Scholar 

  31. Alpern JD, Lopez-Velez R, Stauffer WM. Access to benznidazole for Chagas disease in the United States-cautious optimism? PLoS Negl Trop Dis. 2017;11(9):e0005794. PubMed PMID: 28910299. Pubmed Central PMCID: 5598921.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Richle RW, Raaflaub J. Difference of effective antitrypanosomal dosages of benznidazole in mice and man. Chemotherapeutic and pharmacokinetic results. Acta Trop. 1980;37(3):257–61. PubMed PMID: 6106364.

    CAS  PubMed  Google Scholar 

  33. Chatelain E, Ioset JR. Phenotypic screening approaches for Chagas disease drug discovery. Expert opinion on drug discovery. Expert Opin Drug Discov. 2018;13:141–53. PubMed PMID: 29235363.

    Article  CAS  PubMed  Google Scholar 

  34. Romanha AJ, Castro SL, Soeiro MNC, Lannes-Vieira J, Ribeiro I, Talvani A, et al. In vitro and in vivo experimental models for drug screening and development for Chagas disease. Mem Inst Oswaldo Cruz. 2010;105(2):233–8.

    Article  CAS  PubMed  Google Scholar 

  35. Hall BS, Wilkinson SR. Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. Antimicrob Agents Chemother. 2012;56(1):115–23. PubMed PMID: 22037852. Pubmed Central PMCID: 3256028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Roberts JT, Bleehen NM. Benznidazole with CCNU: a clinical phase I toxicity study. Int J Radiat Oncol Biol Phys. 1985;11(2):331–4. PubMed PMID: 3972652.

    Article  CAS  PubMed  Google Scholar 

  37. Raaflaub J. Multiple-dose kinetics of the trypanosomicide benznidazole in man. Arzneimittelforschung. 1980;30(12):2192–4. PubMed PMID: 6783051.

    CAS  PubMed  Google Scholar 

  38. Workman P, White RA, Walton MI, Owen LN, Twentyman PR. Preclinical pharmacokinetics of benznidazole. Br J Cancer. 1984;50(3):291–303. PubMed PMID: 6466543. Pubmed Central PMCID: 1976805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Roberts JT, Bleehen NM, Lee FY, Workman P, Walton MI. A phase I study of the combination of benznidazole and CCNU in man. Int J Radiat Oncol Biol Phys. 1984;10(9):1745–8. PubMed PMID: 6480457.

    Article  CAS  PubMed  Google Scholar 

  40. Bisio M, Altcheh J, Lattner J, Moscatelli G, Fink V, Burgos JM, et al. Benznidazole treatment of chagasic encephalitis in pregnant woman with AIDS. Emerg Infect Dis. 2013;19(9):1490–2. PubMed PMID: 23965334. Pubmed Central PMCID: 3810932.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Walton MI, Workman P. Nitroimidazole bioreductive metabolism. Quantitation and characterisation of mouse tissue benznidazole nitroreductases in vivo and in vitro. Biochem Pharmacol. 1987;36(6):887–96. PubMed PMID: 3105539.

    Article  CAS  PubMed  Google Scholar 

  42. Workman P, Walton MI, Lee FY. Benznidazole: nitroreduction and inhibition of cytochrome P-450 in chemosensitization of tumour response to cytotoxic drugs. Biochem Pharmacol. 1986;35(1):117–9. PubMed PMID: 3940522.

    Article  CAS  PubMed  Google Scholar 

  43. Streiger ML, del Barco ML, Fabbro DL, Arias ED, Amicone NA. [Longitudinal study and specific chemotherapy in children with chronic Chagas’ disease, residing in a low endemicity area of Argentina]. Estudo longitudinal e quimioterapia especifica em criancas, com doenca de Chagas cronica, residentes em area de baixa endemicidade da Republica Argentina. Rev Soc Bras Med Trop. 2004;37(5):365–75.

    Article  PubMed  Google Scholar 

  44. Alvarez MG, Vigliano C, Lococo B, Bertocchi G, Viotti R. Prevention of congenital Chagas disease by Benznidazole treatment in reproductive-age women. An observational study. Acta Trop. 2017;174:149–52. PubMed PMID: 28720492.

    Article  CAS  PubMed  Google Scholar 

  45. Bertocchi GL, Vigliano CA, Lococo BG, Petti MA, Viotti RJ. Clinical characteristics and outcome of 107 adult patients with chronic Chagas disease and parasitological cure criteria. Trans R Soc Trop Med Hyg. 2013;107(6):372–6. PubMed PMID: 23612468.

    Article  PubMed  Google Scholar 

  46. Viotti R, Vigliano C, Lococo B, Bertocchi G, Alvarez M, Laucella S, et al. Tratamiento antiparasitario en la enfermedad de Chagas. Enferm Emerg. 2008;10(Suppl 1):10–3.

    Google Scholar 

  47. Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med. 2006;144(10):724–34. PubMed PMID: 16702588.

    Article  CAS  PubMed  Google Scholar 

  48. Sosa-Estani S, Armenti A, Araujo G, Viotti R, Lococo B, Ruiz Vera B, et al. Tratamiento de Chagas con benznidazol y ácido tióctico. Medicina (Buenos Aires). 2004;64(1):1–6.

    Google Scholar 

  49. Viotti R, Vigliano C, Armenti H, Segura E. Treatment of chronic Chagas’ disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J. 1994;127(1):151–62. PubMed PMID: 8273735.

    Article  CAS  PubMed  Google Scholar 

  50. Morillo CA, Waskin H, Sosa-Estani S, Del Carmen Bangher M, Cuneo C, Milesi R, et al. Benznidazole and posaconazole in eliminating parasites in asymptomatic T. cruzi carriers: the STOP-CHAGAS trial. J Am Coll Cardiol. 2017;69(8):939–47. PubMed PMID: 28231946.

    Article  CAS  PubMed  Google Scholar 

  51. Sguassero Y, Cuesta CB, Roberts KN, Hicks E, Comande D, Ciapponi A, et al. Course of chronic Trypanosoma cruzi Infection after treatment based on parasitological and serological tests: a systematic review of follow-up studies. PLoS One. 2015;10(10):e0139363. PubMed PMID: 26436678. Pubmed Central PMCID: 4593559.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Carlier Y, Torrico F, Sosa-Estani S, Russomando G, Luquetti A, Freilij H, et al. Congenital Chagas disease: recommendations for diagnosis, treatment and control of newborns, siblings and pregnant women. PLoS Negl Trop Dis. 2011;5(10):e1250. PubMed PMID: 22039554. Pubmed Central PMCID: 3201907.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Coura JR, de Abreu LL, Willcox HP, Petana W. [Comparative controlled study on the use of benznidazole, nifurtimox and placebo, in the chronic form of Chagas’ disease, in a field area with interrupted transmission. I. Preliminary evaluation]. Estudo comparativo controloado com emprego de benznidazole, nifurtimox e placebo, na forma cronica da doenca de Chagas; em uma area de campo com transmissao interrompida. I. Avalicao preliminar. Rev Soc Bras Med Trop. 1997;30(2):139–44.

    Article  CAS  PubMed  Google Scholar 

  54. Gallerano RR, Sosa RR. Estudio de intervención en la evolución natural de la enfermedad de Chagas. Evaluación del tratamiento antiparasitario específico. Estudio retrospectivo-prospectivo de terapéutica antiparasitaria. Rev Fac Cien Med Univ Nac Cordoba. 2000;57(2):135–62.

    CAS  PubMed  Google Scholar 

  55. de Castro AM, Luquetti AO, Rassi A, Chiari E, Galvao LM. Detection of parasitemia profiles by blood culture after treatment of human chronic Trypanosoma cruzi infection. Parasitol Res. 2006;99(4):379–83. PubMed PMID: 16570199.

    Article  PubMed  Google Scholar 

  56. Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Medecins Sans Frontieres. PLoS Negl Trop Dis. 2009;3(7):e488. PubMed PMID: 19582142. Pubmed Central PMCID: 2700957.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Molina I, Salvador F, Sanchez-Montalva A, Artaza MA, Moreno R, Perin L, et al. Pharmacokinetics of benznidazole in healthy volunteers and implications in future clinical trials. Antimicrob Agents Chemother. 2017;61(4):e01912–6. PubMed PMID: 28167552. Pubmed Central PMCID: 5365666.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Soy D, Aldasoro E, Guerrero L, Posada E, Serret N, Mejia T, et al. Population pharmacokinetics of benznidazole in adult patients with Chagas disease. Antimicrob Agents Chemother. 2015;59(6):3342–9. PubMed PMID: 25824212. Pubmed Central PMCID: 4432184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr, Rosas F, et al. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med. 2015;373(14):1295–306. PubMed PMID: 26323937.

    Article  CAS  PubMed  Google Scholar 

  60. Alvarez MG, Hernandez Y, Bertocchi G, Fernandez M, Lococo B, Ramirez JC, et al. New scheme of intermittent benznidazole administration in patients chronically infected with Trypanosoma cruzi: a pilot short-term follow-up study with adult patients. Antimicrob Agents Chemother. 2016;60(2):833–7. PubMed PMID: 26596935. Pubmed Central PMCID: 4750658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Morillo CA, Marin-Neto JA, Avezum A. Benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med. 2016;374(2):189–90. PubMed PMID: 26760092.

    PubMed  Google Scholar 

  62. Rassi A Jr, Marin Neto JA, Rassi A. Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial. Mem Inst Oswaldo Cruz. 2017;112(3):224–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sperandio da Silva GM, Mediano MFF, Hasslocher-Moreno AM, Holanda MT, Silvestre de Sousa A, Sangenis LHC, et al. Benznidazole treatment safety: the Medecins Sans Frontieres experience in a large cohort of Bolivian patients with Chagas’ disease. J Antimicrob Chemother. 2017;72(9):2596–601. PubMed PMID: 28645201.

    Article  PubMed  CAS  Google Scholar 

  64. Yun O, Priotto G, Tong J, Flevaud L, Chappuis F. NECT is next: implementing the new drug combination therapy for Trypanosoma brucei gambiense sleeping sickness. PLoS Negl Trop Dis. 2010;4(5):e720. PubMed PMID: 20520803. Pubmed Central PMCID: 2876135.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Duhm B, Maul W, Medenwald H, Patzschke K, Wegner LA. Investigations on the pharmacokinetics of nifurtimox-35 S in the rat and dog. Arzneimittelforschung. 1972;22(9):1617–24. PubMed PMID: 4630484.

    CAS  PubMed  Google Scholar 

  66. Haberkorn A, Gonnert R. Animal experimental investigation into the activity of nifurtimox against Trypanosoma cruzi. Arzneimittelforschung. 1972;22(9):1570–82. PubMed PMID: 4630483.

    CAS  PubMed  Google Scholar 

  67. Gonzalez-Martin G, Thambo S, Paulos C, Vasquez I, Paredes J. The pharmacokinetics of nifurtimox in chronic renal failure. Eur J Clin Pharmacol. 1992;42(6):671–3. PubMed PMID: 1623911.

    Article  CAS  PubMed  Google Scholar 

  68. Paulos C, Paredes J, Vasquez I, Kunze G, Gonzalez-Martin G. High-performance liquid chromatographic determination of nifurtimox in human serum. J Chromatogr. 1988;433:359–62. PubMed PMID: 3235567.

    Article  CAS  PubMed  Google Scholar 

  69. Paulos C, Paredes J, Vasquez I, Thambo S, Arancibia A, Gonzalez-Martin G. Pharmacokinetics of a nitrofuran compound, nifurtimox, in healthy volunteers. Int J Clin Pharmacol Ther Toxicol. 1989;27(9):454–7. PubMed PMID: 2807618.

    CAS  PubMed  Google Scholar 

  70. Saulnier Sholler GL, Bergendahl GM, Brard L, Singh AP, Heath BW, Bingham PM, et al. A phase 1 study of nifurtimox in patients with relapsed/refractory neuroblastoma. J Pediatr Hematol Oncol. 2011;33(1):25–30. PubMed PMID: 21063221.

    Article  PubMed  Google Scholar 

  71. Medenwald H, Brandau K, Schlossmann K. Quantitative determination of nifurtimox in body fluids of rat, dog and man. Arzneimittel-Forschung. 1972;22(9):1613–7. PubMed PMID: 4678720.

    CAS  PubMed  Google Scholar 

  72. Gonzalez-Martin G, Paulos C, Guevara A, Ponce G. Disposition of nifurtimox and metabolite activity against Trypanosoma cruzi using rat isolated perfused liver. J Pharm Pharmacol. 1994;46(5):356–9. PubMed PMID: 8083806.

    Article  CAS  PubMed  Google Scholar 

  73. Letelier ME, Izquierdo P, Godoy L, Lepe AM, Faundez M. Liver microsomal biotransformation of nitro-aryl drugs: mechanism for potential oxidative stress induction. J Appl Toxicol. 2004;24(6):519–25. PubMed PMID: 15558828.

    Article  CAS  PubMed  Google Scholar 

  74. Masana M, de Toranzo EG, Castro JA. Studies on nifurtimox nitroreductase activity in liver and other rat tissues. Arch Int Pharmacodynam Ther. 1984;270(1):4–10. PubMed PMID: 6497502.

    CAS  Google Scholar 

  75. Garcia-Bournissen F, Altcheh J, Panchaud A, Ito S. Is use of nifurtimox for the treatment of Chagas disease compatible with breast feeding? A population pharmacokinetics analysis. Arch Dis Child. 2010;95(3):224–8. PubMed PMID: 19948512.

    Article  PubMed  Google Scholar 

  76. Watson CP, Dogruel M, Mihoreanu L, Begley DJ, Weksler BB, Couraud PO, et al. The transport of nifurtimox, an anti-trypanosomal drug, in an in vitro model of the human blood-brain barrier: evidence for involvement of breast cancer resistance protein. Brain Res. 2012;1436:111–21. PubMed PMID: 22200378. Pubmed Central PMCID: 3281990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cancado JA, Salgado AA, Marra UD, Alvares JM, Machado JR. [Clinical therapeutic trial in chronic Chagas’ disease using nifurtimox in 3 schedules of long duration]. Ensaio terapeutico cl’inico na doenca de Chagas cronica com o nifurtimox em tres esquemas de dura coa prolongada. Rev Inst Med Trop Sao Paulo. 1975;17(2):111–27.

    CAS  PubMed  Google Scholar 

  78. Freilij H, Altcheh J. Congenital Chagas’ disease: diagnostic and clinical aspects. Clin Infect Dis. 1995;21(3):551–5. PubMed PMID: 8527542.

    Article  CAS  PubMed  Google Scholar 

  79. Coura JR. [Current prospects of specific treatment of Chagas’ disease] Perspectivas actuales del tratamiento especifico de la enfermedad de Chaga. Bol Chil Parasitol. 1996;51(3–4):69–75. PubMed PMID: 9302778.

    CAS  PubMed  Google Scholar 

  80. Jackson Y, Alirol E, Getaz L, Wolff H, Combescure C, Chappuis F. Tolerance and safety of nifurtimox in patients with chronic Chagas disease. Clin Infect Dis. 2010;51(10):e69–75. PubMed PMID: 20932171.

    Article  CAS  PubMed  Google Scholar 

  81. Forsyth CJ, Hernandez S, Olmedo W, Abuhamidah A, Traina MI, Sanchez DR, et al. Safety profile of nifurtimox for treatment of Chagas disease in the United States. Clin Infect Dis. 2016;63(8):1056–62. PubMed PMID: 27432838. Pubmed Central PMCID: 5036918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Alarcon de Noya B, Ruiz-Guevara R, Noya O, Castro J, Ossenkopp J, Diaz-Bello Z, et al. Long-term comparative pharmacovigilance of orally transmitted Chagas disease: first report. Expert Rev Anti-Infect Ther. 2017;15(3):319–25. PubMed PMID: 28132566.

    Article  CAS  PubMed  Google Scholar 

  83. Perez-Molina JA, Sojo-Dorado J, Norman F, Monge-Maillo B, Diaz-Menendez M, Albajar-Vinas P, et al. Nifurtimox therapy for Chagas disease does not cause hypersensitivity reactions in patients with such previous adverse reactions during benznidazole treatment. Acta Trop. 2013;127(2):101–4. PubMed PMID: 23583863.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, Argentina

    Facundo Garcia-Bournissen

  2. Instituto Multidisciplinario de Investigación en Patologías Pediátricas (IMIPP-GCBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Facundo Garcia-Bournissen

Authors
  1. Facundo Garcia-Bournissen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, Argentina

    Jaime Marcelo Altcheh

  2. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, Argentina

    Hector Freilij

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Garcia-Bournissen, F. (2019). Clinical Pharmacology of Drugs for the Treatment of Chagas Disease. In: Altcheh, J., Freilij, H. (eds) Chagas Disease. Birkhäuser Advances in Infectious Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-00054-7_14

Download citation

Publish with us

Policies and ethics

Search

Navigation