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Efficacy, safety and pharmacokinetics of 1,2,4-trioxolane OZ78 against an experimental infection with Fasciola hepatica in sheep

Keiser, Jennifer and Kirchhofer, Carla and Haschke, Manuel and Huwyler, Jörg and Dong, Yuxiang and Vennerstrom, Jonathan L. and Vanhoff, Kathleen and Kaminsky, Ronald and Malikides, Nick. (2010) Efficacy, safety and pharmacokinetics of 1,2,4-trioxolane OZ78 against an experimental infection with Fasciola hepatica in sheep. Veterinary parasitology, Vol. 173, H. 3-4. pp. 228-235.

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Official URL: http://edoc.unibas.ch/dok/A5840217

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Abstract

The synthetic peroxide OZ78 is an effective flukicide in the rodent model, but the potential of OZ78 in target animals has not been studied to date. In the present study, OZ78 was administered at 50mg/kg orally and subcutaneously to sheep harbouring an experimental Fasciola hepatica infection and the efficacy, tolerability and pharmacokinetic profiles were monitored. OZ78 given orally or subcutaneously revealed no effect neither on faecal egg counts nor on worm burdens. Apart from significant subcutaneous swelling at the injection sites of most of the treated animals, no other treatment related adverse events occurred. OZ78 had no significant effect on any haematological, coagulation or clinical chemistry variables tested. Following oral administration, a mean C(max) of 45.8±13 ?g/ml was reached after 1h. An estimated elimination half-life of 1.0 h and a mean AUC of 116.2±47 ?g min/ml was calculated for the oral administration. Following subcutaneous treatment with OZ78 C(max) and t(max) were 13.7±6.1?g/ml and 0.9±0.4h, respectively. The ? and ? half-lives were 4.5±4.3 h and 56.5±36 h, respectively and the mean AUC was 219.1±74 ?g min/ml. Further studies are needed to determine whether the excellent activity observed with OZ78 in the rat model can be translated into efficacy in larger mammals.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Huwyler, Jörg and Keiser, Jennifer and Kirchhofer, Carla
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0304-4017
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:10
Deposited On:08 Jun 2012 06:51

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