Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model.
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 trea...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3117839?pdf=render |
| _version_ | 1811213403304230912 |
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| author | Kirsten Gillingwater Carlos Gutierrez Arlene Bridges Huali Wu Stijn Deborggraeve Rosine Ali Ekangu Arvind Kumar Mohamed Ismail David Boykin Reto Brun |
| author_facet | Kirsten Gillingwater Carlos Gutierrez Arlene Bridges Huali Wu Stijn Deborggraeve Rosine Ali Ekangu Arvind Kumar Mohamed Ismail David Boykin Reto Brun |
| author_sort | Kirsten Gillingwater |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T05:45:05Z |
| format | Article |
| id | doaj.art-2e6941434eff422b983015e36822cc05 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T05:45:05Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2e6941434eff422b983015e36822cc052022-12-22T03:45:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2083610.1371/journal.pone.0020836Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model.Kirsten GillingwaterCarlos GutierrezArlene BridgesHuali WuStijn DeborggraeveRosine Ali EkanguArvind KumarMohamed IsmailDavid BoykinReto BrunThree 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.http://europepmc.org/articles/PMC3117839?pdf=render |
| spellingShingle | Kirsten Gillingwater Carlos Gutierrez Arlene Bridges Huali Wu Stijn Deborggraeve Rosine Ali Ekangu Arvind Kumar Mohamed Ismail David Boykin Reto Brun Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. PLoS ONE |
| title | Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. |
| title_full | Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. |
| title_fullStr | Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. |
| title_full_unstemmed | Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. |
| title_short | Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. |
| title_sort | efficacy study of novel diamidine compounds in a trypanosoma evansi goat model |
| url | http://europepmc.org/articles/PMC3117839?pdf=render |
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