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

K Gillingwater, C Gutierrez, A Bridges, H Wu, S Deborggraeve, RA Ekangu, A Kumar, M Ismail, D Boykin, R Brun

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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.
    Original languageEnglish
    JournalPLoS ONE
    Volume6
    Issue number6
    Pages (from-to)e20836
    Number of pages6
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Animal diseases
    • Surra
    • Trypanosoma evansi
    • Goats
    • Treatment
    • Modeling
    • Assessment
    • Toxicity
    • Efficacy
    • Diadimine
    • Diminazene
    • Drug development
    • Pharmacokinetics
    • Laboratory techniques and procedures
    • Card agglutination test
    • CATT
    • Polymerase chain reaction
    • PCR
    • Islands
    • Spain
    • Europe-South
    • Africa-West

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