Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-18T01:20:45.834Z Has data issue: false hasContentIssue false
  • English
  • Français

Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverriniin vitro and in vivo

Published online by Cambridge University Press:  15 August 2012

J. Keiser ,
R. Adelfio ,
M. Vargas ,
P. Odermatt  and
S. Tesana
J. Keiser*
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland University of Basel, CH-4003 Basel, Switzerland
R. Adelfio
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland University of Basel, CH-4003 Basel, Switzerland
M. Vargas
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland University of Basel, CH-4003 Basel, Switzerland
P. Odermatt
Affiliation:
University of Basel, CH-4003 Basel, Switzerland Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland
S. Tesana
Affiliation:
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
*
*Fax: +41 61 284-8105 E-mail: jennifer.keiser@unibas.ch
Get access Rights & Permissions [Opens in a new window]

Abstract

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine–praziquantel combinations against O. viverriniin vitro and in vivo. The IC50 values of 0.16 μg/ml and 0.05 μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverriniin vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50= 0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191 mg/kg and 147 mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38–62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrini.

Type
Research Papers
Information
Journal of Helminthology , Volume 87 , Issue 2 , June 2013 , pp. 252 - 256
Copyright
Copyright © Cambridge University Press 2012 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Botros, S., El-Lakkany, N., Seif El-Din, S.H., Sabra, A.N. & Ibrahim, M. (2011) Comparative efficacy and bioavailability of different praziquantel brands. Experimental Parasitology 127, 515–521.CrossRefGoogle ScholarPubMed
Chou, T.C. (2010) Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Research 70, 440–446.CrossRefGoogle ScholarPubMed
Fürst, T., Keiser, J. & Utzinger, J. (2012a) Global burden of human food-borne trematodiasis: a systematic review and meta-analysis. Lancet Infectious Diseases 12, 210–221.CrossRefGoogle ScholarPubMed
Fürst, T., Sayasone, S., Odermatt, P., Keiser, J. & Utzinger, J. (2012b) Manifestation, diagnosis, and management of food-borne trematodiasis. British Medical Journal 344, e4093.CrossRefGoogle Scholar
Harasym, T., Liboiron, B. & Mayer, L. (2010) Drug ratio-dependent antagonism: a new category of multidrug resistance and strategies for its circumvention. Methods in Molecular Biology 596, 291–323.CrossRefGoogle ScholarPubMed
Keiser, J. & Utzinger, J. (2005) Emerging foodborne trematodiasis. Emerging Infectious Diseases 11, 1507–1514.CrossRefGoogle ScholarPubMed
Keiser, J. & Utzinger, J. (2009) Food-borne trematodiases. Clinical Microbiology Reviews 22, 466–483.CrossRefGoogle ScholarPubMed
Keiser, J. & Utzinger, J. (2010) The drugs we have and the drugs we need against major helminth infections. Advances in Parasitology 73, 197–230.CrossRefGoogle ScholarPubMed
Keiser, J., Xiao, S.H., Xue, J., Chang, Z.S., Odermatt, P., Tesana, S., Tanner, M. & Utzinger, J. (2006) Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis viverrini in rodent models. International Journal of Antimicrobial Agents 28, 370–373.CrossRefGoogle ScholarPubMed
Keiser, J., Xiao, S.H., Chollet, J., Tanner, M. & Utzinger, J. (2007) Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni, Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini. Antimicrobial Agents and Chemotherapy 51, 1096–1098.CrossRefGoogle ScholarPubMed
Keiser, J., Xiao, S.H., Smith, T.A. & Utzinger, J. (2009) Combination chemotherapy against Clonorchis sinensis: experiments with artemether, artesunate, OZ78, praziquantel, and tribendimidine in a rat model. Antimicrobial Agents and Chemotherapy 53, 3770–3776.CrossRefGoogle ScholarPubMed
Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M. & Altman, D.G. (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biology 8, e1000412.CrossRefGoogle ScholarPubMed
Sithithaworn, P., Andrews, R.H., Van De, N., Wongsaroj, T., Sinuon, M., Odermatt, P., Nawa, Y., Liang, S., Brindley, P.J. & Sripa, B. (2012) The current status of opisthorchiasis and clonorchiasis in the Mekong Basin. Parasitology International 61, 10–16.CrossRefGoogle ScholarPubMed
Soukhathammavong, P., Odermatt, P., Sayasone, S., Vonghachack, Y., Vounatsou, P., Hatz, C., Akkhavong, K. & Keiser, J. (2011) Efficacy and safety of mefloquine, artesunate, mefloquine–artesunate, tribendimidine, and praziquantel in patients with Opisthorchis viverrini: a randomised, exploratory, open-label, phase 2 trial. Lancet Infectious Diseases 11, 110–118.CrossRefGoogle ScholarPubMed
Sripa, B. & Pairojkul, C. (2008) Cholangiocarcinoma: lessons from Thailand. Current Opinion Gastroenterology 24, 349–356.CrossRefGoogle ScholarPubMed
Sripa, B., Kaewkes, S., Intapan, P.M., Maleewong, W. & Brindley, P.J. (2010) Food-borne trematodiases in Southeast Asia: epidemiology, pathology, clinical manifestation and control. Advances in Parasitology 72, 305–350.CrossRefGoogle ScholarPubMed
Yuan, G., Xu, J., Qu, T., Wang, B., Zhang, R., Wei, C. & Guo, R. (2010) Metabolism and disposition of tribendimidine and its metabolites in healthy Chinese volunteers. Drugs in R&D 10, 83–90.Google ScholarPubMed