Synthesis and detection of toltrazuril sulfone and its pharmacokinetics in horses following administration in dimethylsulfoxide.

This research explores the use of the solvent dimethylsulfoxide (DMSO) to enhance the oral absorption and bioavailability of triazine-based antiprotozoal agent, toltrazuril sulfone (Ponazuril), in horses. The study concludes that DMSO significantly increases the oral bioavailability of Ponazuril, suggesting its effectiveness in treating horses, particularly in cases of Equine Protozoal Myeloencephalitis.

The importance of solvents in drug absorption

• The study begins by discussing the challenge of administering lipophylic triazine-based antiprotozoal agents orally. Despite their anticipated high absorption due to their lipid solubility, the extreme lipid solubility of these agents can dissolve poorly in gastrointestinal (GI) fluids, leading to low absorption and bioavailability.
• The research identifies the need for a solvent with minuscule or no toxicity that maintains triazine agents in solution, therefore increasing their rate of absorption following oral administration.

Role and effectiveness of dimethylsulfoxide (DMSO)

• The study puts to test the effectiveness of DMSO as a solvent. It demonstrates that DMSO increases the oral bioavailability of toltrazuril sulfone (Ponazuril) threefold as compared to when toltrazuril sulfone is suspended in water.
• According to a cross-over study of toltrazuril sulfone formulated in DMSO, the absolute oral bioavailability of the agent in DMSO was found to be 71%.

Implications of using DMSO to formulate toltrazuril sulfone

• The high bioavailability achieved from using DMSO as a solvent suggests that its daily oral administration will routinely yield effective plasma and cerebral spinal fluid (CSF) concentrations in all horses treated.
• The study indicates that this improved method of administration and formulation would potentially allow clinicians to administer loading doses of toltrazuril sulfone in acute cases of Equine Protozoal Myeloencephalitis, a pathogenic infection in horses.
• Moreover, DMSO-based toltrazuril sulfone could be mixed with feed adhering to the FDA’s recommendations for the permissible levels of DMSO in pharmaceutical preparations. This highlights the practical benefits of the approach.