Toltrazuril sulfone sodium salt: Synthesis, analytical detection, and pharmacokinetics in the Horse

Levent Dirikolu, W. Karpiesiuk, A. F. Lehner, T. Tobin

Research output: Contribution to journalArticle

Abstract

Toltrazuril sulfone (ponazuril) is a triazine-based antiprotozoal agent with clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, we synthesized and determined the bioavailability of a sodium salt formulation of toltrazuril sulfone that can be used for the treatment and prophylaxis of EPM in horses. Toltrazuril sulfone sodium salt was rapidly absorbed, with a mean peak plasma concentration of 2400±169 (SEM) ng/mL occurring at 8h after oral-mucosal dosing and was about 56% bioavailable compared with the i.v. administration of toltrazuril sulfone in dimethylsulfoxide (DMSO). The relative bioavailability of toltrazuril sulfone suspended in water compared with toltrazuril sulfone sodium salt was 46%, indicating approximately 54% less oral bioavailability of this compound suspended in water. In this study, we also investigated whether this salt formulation of toltrazuril sulfone can be used as a feed additive formulation without significant reduction in oral bioavailability. Our results indicated that toltrazuril sulfone sodium salt is relatively well absorbed when administered with feed with a mean oral bioavailability of 52%. Based on these data, repeated oral administration of toltrazuril sulfone sodium salt with or without feed will yield effective plasma and cerebrospinal fluid (CSF) concentrations of toltrazuril sulfone for the treatment and prophylaxis of EPM and other protozoal diseases of horses and other species. As such, toltrazuril sulfone sodium salt has the potential to be used as feed additive formulations for both the treatment and prophylaxis of EPM and various other apicomplexan diseases.

Original languageEnglish (US)
Pages (from-to)265-274
Number of pages10
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume35
Issue number3
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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