Quantitative assessment of torasemide ototoxicity

Area of Science:

• Ototoxicology
• Pharmacology
• Veterinary Medicine

Background:

• Loop diuretics can cause ototoxicity, a potential side effect impacting hearing.
• Torasemide is a newer loop diuretic with a distinct chemical structure.
• Quantitative assessment of ototoxicity is crucial for drug safety evaluation.

Purpose of the Study:

• To quantitatively assess the ototoxic potential of torasemide in a feline model.
• To determine the toxic dose 50 (TD50) for torasemide-induced hearing loss in cats.
• To evaluate the ototoxic effects of torasemide's primary human metabolite (M5).

Main Methods:

• Quantitative ototoxicity testing in cats using audiometric measurements.
• Determination of the toxic dose 50 (TD50) for torasemide.
• Assessment of hearing recovery post-torasemide administration.
• Testing the ototoxicity of torasemide metabolite M5 at high doses.

Main Results:

• The TD50 for torasemide in cats was determined to be 20.8 mg/kg.
• Torasemide's TD50 was not significantly different from that of furosemide (18.37 mg/kg).
• A tendency for hearing function recovery was observed after acute torasemide exposure.
• Torasemide metabolite M5 demonstrated no ototoxic effects, even at excessive doses.
• Pretreatment with torasemide at doses exceeding TD50 did not result in permanent hearing impairment.

Conclusions:

• Torasemide exhibits a low ototoxic potential in cats, comparable to furosemide.
• Hearing function appears to recover after acute torasemide exposure.
• The main human metabolite of torasemide (M5) is not ototoxic.
• Torasemide is unlikely to cause permanent hearing damage in cats.