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Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model

Gillingwater, K. and Gutierrez, C. and Bridges, A. and Wu, H. and Deborggraeve, S. and Ali Ekangu R., and Kumar, A. and Ismail, M. and Boykin, D. and Brun, R.. (2011) Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. PLoS one, Vol. 6, H. 6 , e20836.

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Official URL: http://edoc.unibas.ch/dok/A6002185

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Abstract

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Brun, Reto
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:PubMed Central
ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:10
Deposited On:11 Oct 2012 15:30

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