title: New therapeutic approaches for equine protozoal myeloencephalitis: pharmacokinetics of diclazuril sodium salts in horses.
abstract: Diclazuril is a triazine-based antiprotozoal agent which may have clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, the use of the sodium salt diclazuril to increase the apparent bioavailability of diclazuril for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases is described. In this study, diclazuril sodium salt was synthesized and administered to horses as diclazuril sodium salt formulations. The absorption, distribution, and clearance of diclazuril sodium salt in the horse are described. Diclazuril was rapidly absorbed, with peak plasma concentrations occurring at 8-24 hours following an oral mucosal administration of diclazuril sodium salt. The mean oral bioavailability of diclazuril as Clinacox was 9.5% relative to oral mucosal administration of diclazuril sodium salt. Additionally, diclazuril in DMSO administered orally was 50% less bioavailable than diclazuril sodium salt following an oral mucosal administration. It was also shown that diclazuril sodium salt has the potential to be used as a feed additive for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases.
authors.affiliation: Department of Veterinary Science, The Maxwell H. Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA.
authors.forename: Levent
authors.initials: L
authors.lastname: Dirikolu
authors.forename: Wojciech
authors.initials: W
authors.lastname: Karpiesiuk
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Lehner
authors.forename: Charlie
authors.initials: C
authors.lastname: Hughes
authors.forename: William E
authors.initials: WE
authors.lastname: Woods
authors.forename: John D
authors.initials: JD
authors.lastname: Harkins
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyles
authors.forename: Alfonza
authors.initials: A
authors.lastname: Atkinson
authors.forename: David E
authors.initials: DE
authors.lastname: Granstrom
authors.forename: Thomas
authors.initials: T
authors.lastname: Tobin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D020808:Central Nervous System Protozoal Infections / Q000188:drug therapy / Q000662:veterinary; D002626:Chemistry, Pharmaceutical; D003049:Coccidiostats / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004121:Dimethyl Sulfoxide; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy; D006736:Horses / Q000097:blood / Q000378:metabolism*; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012492:Salts; D012964:Sodium; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D003049:Coccidiostats; D009570:Nitriles; D012492:Salts; D014227:Triazines; D012964:Sodium; C057884:diclazuril; D004121:Dimethyl Sulfoxide