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Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations

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Abstract

The pharmacokinetic (PK) behaviour and clinical efficacy of albendazole (ABZ) against hydatid cysts in mice were assessed after treatment with two different ABZ pharmaceutical formulations. BalbC mice received ABZ (0.5 mg/kg) prepared either as solution or suspension (50 μg/ml) for oral administration (PK study). Blood samples were collected up to 16 h post-treatment and processed to measure ABZ/metabolites concentrations in plasma. The clinical efficacy assessment was performed in BalbC mice infected 8 months earlier with Echinococcus granulosus protoscoleces. Infected animals were allocated into three experimental treatment groups: (a) untreated control, (b) ABZ-solution treated, (c) ABZ-suspension treated. Both treated groups received ABZ (0.5 mg/kg) administered under two different therapeutic schemes: dosing every 48 h over 30 days (regimen I) or treated every 12 h during 15 days (regimen II). Experimental mice were sacrificed 12 h after treatment, and cysts were recovered, weighed and processed for transmission electron microscopy. Enhanced ABZ sulphoxide (the main ABZ metabolite) concentration profiles were measured in animals treated with the ABZ solution. Any positive clinical response was obtained after treatment every 48 h (30 days therapy). However, consistent with the observed PK results, both ABZ formulations were clinically effective in infected mice treated with a 12-h dosing interval (15 days therapy).

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References

  • Ammann R, Eckert J (1995) Clinical diagnosis and treatment of echinococcosis in humans. In: Thompson RCA, Limbery AJ (eds) Echinococcus and hydatid disease. CAB International, Wallingford, UK, pp 441–463

    Google Scholar 

  • Bartoloni C, Tricerri A, Guidi L, Gambassi G (1992) The efficacy of chemotherapy with mebendazole in human cystic echinococcosis: long-term follow-up of 52 patients. Ann Trop Med Parasitol 86:249–256

    PubMed  CAS  Google Scholar 

  • Castillo JA, Palomo-Canales J, García JJ, Lastres JL, Torrado JJ (1999) Preparation and characterization of albendazole b-cyclodextrin complexes. Drug Dev Ind Pharm 25:1241–1248

    Article  PubMed  CAS  Google Scholar 

  • Ceballos L, Alvarez LI, Sanchez Bruni SF, Elissondo C, Dopchiz M, Denegri G, Torrado JJ, Lanusse CE (2006) Development of a cyclodextrin-based flubendazole formulation to control secondary echinococcosis: pharmacokinetics, hydatid cyst morphology and efficacy in mice. J Vet Pharmacol Ther 29:85–86

    Google Scholar 

  • Davis A, Pawlowski ZS, Dixon H (1986) Multicenter trials of benzimidazole–carbamates in human echinococcosis. Bull World Health Organ 64:383–388

    PubMed  CAS  Google Scholar 

  • Davis A, Dixon H, Pawlowski ZS (1989) Multicentre clinical trials of benzimidazole carbamates in human cystic echinococcosis (phase 2). Bull World Health Organ 67:503–508

    PubMed  CAS  Google Scholar 

  • Dayan AD (2003) Albendazole, mebendazole and praziquantel. Review of non-clinical toxicity and pharmacokinetics. Acta Trop 86:141–159

    Article  PubMed  CAS  Google Scholar 

  • Eckert J, Deplazes P (2004) Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev 17:107–135

    Article  PubMed  Google Scholar 

  • Elissondo C, Dopchiz M, Brasesco M, Denegri G (2004) Echinococcus granulosus: first report of microcysts formation from protoscoleces of cattle origin using the in vitro vesicular culture technique. Parasite 11:415–418

    PubMed  CAS  Google Scholar 

  • Elissondo C, Ceballos L, Dopchiz M, Andresiuk V, Alvarez LI, Sánchez Bruni SF, Lanusse CE, Denegri G (2007) In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes. Parasitol Res 100:1003–1009

    Article  PubMed  CAS  Google Scholar 

  • El-On J (2003) Benzimidazole treatment of cystic echinococcosis. Acta Trop 85:243–252

    Article  PubMed  CAS  Google Scholar 

  • Evrard B, Chiap P, DeTullio P, Ghalmid F, Piela G, Van Heesa T, Crommen J, Losson B, Delattre L (2002) Oral bioavailability in sheep of albendazole from a suspensión and from a solution containing hydroxypropyl-b-cyclodextrin. J Control Release 85:45–50

    Article  PubMed  CAS  Google Scholar 

  • García JJ, Bolás F, Torrado JJ (2003) Bioavailability and efficacy characteristics of two different oral liquid formulations of albendazole. Int J Pharm 250:351–358

    Article  PubMed  Google Scholar 

  • Garcıa-Rodriguez J, Torrado JJ, Bolas F (2001) Improving bioavailability and anthelmintic activity of albendazole by preparing albendazole–cyclodextrin complexes. Parasite 8:188–190

    Google Scholar 

  • Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker, New York

    Google Scholar 

  • Horton RJ (2003) Albendazole for the treatment of echinococcosis. Fundam Clin Pharmacol 17:205–212

    Article  PubMed  CAS  Google Scholar 

  • Jenkins DJ, Romig T, Thompson RCA (2005) Emergence/re-emergence of Echinococcus spp.—a global update. Int J Parasitol 35:1205–1219

    Article  PubMed  CAS  Google Scholar 

  • Kohri N, Yamayoshi Y, Xin H, Iseki K, Sato N, Todo S, Miyazaki K (1999) Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique. J Pharm Pharmacol 51:159–164

    Article  PubMed  CAS  Google Scholar 

  • Lanusse CE, Prichard RK (1993) Clinical pharmacokinetics and metabolism of benzimidazole anthelmintics in ruminants. Drug Metab Rev 25:235–279

    Article  PubMed  CAS  Google Scholar 

  • Menezes da Silva A (2003) Hydatid cyst of the liver—criteria for the selection of appropriate treatment. Acta Trop 85:237–242

    Article  PubMed  CAS  Google Scholar 

  • Moro P, Schantz PM (2006) Cystic echinococcosis in the Americas. Parasitol Int 55:181–186

    Article  Google Scholar 

  • Pawlowski ZS, Eckert J, Vuitton DA, Ammann RW, Kern P, Craig PS et al (2001) Echinococcosis in humans: clinical aspects, diagnosis and treatment. In: Eckert J, Gemmell MA, Meslin FX, Pawlowski ZS (eds) WHO/OIE manual on echinococcosis in humans and animals: a public health problem of global concern. World Organisation for Animal Health, Paris, France

    Google Scholar 

  • Recco P, Hornus E, Frejevus J, Micheau P, Bessieres MH, Roques C, Linas MD (1984) Hydatidose pleurale disseminee et hydatidoses hepatiquesTreatment post-operatoire par flubendazole a propos de 3 cas. Bull Soc Fr Parasitol 3:115–118

    Google Scholar 

  • Rippman K, Dietrich M, Kern P (1992) Long-term therapy of cystic liver echinococcosis with mebendazole. Medizin Klin 87:350–354

    Google Scholar 

  • Rodrigues JM, Bories C, Emery I, Fessi H, Devissaguet JP, Liance M (1995) Development of an injectable formulation of albendazole and in vivo evaluation of its efficacy against Echinococcus multilocularis metacestode. Int J Parasitol 12:1437–1441

    Article  Google Scholar 

  • Shuhua X, Jiqing Y, Mingjie W, Pieying J, Fanghua G, Junjie C, Wei J, Hotez P (2002) Augmented bioavailability and cysticidal activity of albendazole reformulated in soybean emulsion in mice infected with Echinococcus granulosus or Echinococcus multilocularis. Acta Trop 82:77–84

    Article  PubMed  Google Scholar 

  • Stettler M, Rossignol JF, Fink R, Walker M, Gottstein B, Merli M, Theurillat R, Thormann W, Dricot E, Segers R, Hemphill A (2004) Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity. Int J Parasitol 34:615–624

    Article  PubMed  CAS  Google Scholar 

  • Teggi A, Lastilla GM, De Rosa F (1993) Therapy of human hydatid disease with mebendazole and albendazole. Antimicrob Agents Chemother 37:1679–1684

    PubMed  CAS  Google Scholar 

  • Thompson D, Geary T (1995) The structure and function of helminth surfaces. In: Harr J, Muller M (eds) Biochemistry and molecular biology of parasites. Academic, London, UK

    Google Scholar 

  • Todorov T, Mechkov G, Georgiev P, Handjiev S, Vutova K, Petkov D et al (1998) Chemotherapy of human cystic hydatid disease: indications, effectiveness, prognosis. Mediterr J Infect Parasitic Diseases 13:89–94

    Google Scholar 

  • World Health Organization Informal Working Group on Echinococcosis (1996) Guideline for treatment of cysts and alveolar echinococcosis in human. Bull World Health Organ. Informal Working Group on Echinococcosis 74:231–242

    Google Scholar 

  • World Health Organization Informal Working Group of Echinococcosis (2001) Puncture, aspiration, injection, re-aspiration. An option for the treatment of cystic echinococcosis. World Health Organization, Geneva, Switzerland, pp 1–40

    Google Scholar 

  • Xiao SH, You JQ, Yang YQ, Guo HF, Zhang CW, Chai JJ, Zhang WL (1988) Histological alterations and drug concentrations in endocysts and cysts fluid of hydatid cysts harboring in mice treated with praziquantel. Acta Pharmacol Sin 9:461–464

    CAS  Google Scholar 

Download references

Acknowledgment

This work was partially supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Promoción Científica y Técnica (ANPCyT), both from Argentina.

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Authors and Affiliations

  1. Departamento de Fisiopatología, Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, 7000, Tandil, Argentina

    Laura Ceballos, Laura Moreno, Sergio Sánchez Bruni , Luis Alvarez & Carlos Lanusse

  2. Departamento de Biología, Laboratorio de Zoonosis Parasitarias, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Funes 3250, 7600, Mar del Plata, Argentina

    Celina Elissondo, Marcela Dopchiz & Guillermo Denegri

  3. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Laura Ceballos, Celina Elissondo, Laura Moreno, Marcela Dopchiz, Sergio Sánchez Bruni , Guillermo Denegri, Luis Alvarez & Carlos Lanusse

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  1. Laura Ceballos
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  2. Celina Elissondo
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  3. Laura Moreno
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  4. Marcela Dopchiz
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  5. Sergio Sánchez Bruni
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  6. Guillermo Denegri
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  7. Luis Alvarez
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  8. Carlos Lanusse
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Correspondence to Laura Ceballos.

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Ceballos, L., Elissondo, C., Moreno, L. et al. Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations. Parasitol Res 103, 355–362 (2008). https://doi.org/10.1007/s00436-008-0980-x

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  • DOI: https://doi.org/10.1007/s00436-008-0980-x

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