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Ocular toxicity in beagle dogs with an experimental fluoromethane-sulfonanilide sympathomimetic agent
Abstract:
ocular lesions were detected in Beagle dogs receiving high doses of BA6650, an experimental fluoremethane-sulfonanilide sympathomimetic agent, during a preclinical safety evaluation study. The oral dose of BA6650 was increased during the 14-day study from 20 mg/kg twice daily (bid) for days 1-3 to 30 mg/kg bid for days 4-6 and finally to 40 mg/kg bid for days 7-14. Two males and two females received BA6650 while one male and one female were not dosed. Intraocular pressure in the untreated controls fluctuated during the study between 17 and 22 mmHg. Intraocular pressure decreased in 3 of 4 BA6650 treated dogs from an initial mean value of 17 to a final mean value of 8 mmHg. Ocular lesions consisting of conjunctival hyperemia, corneal opacities, epiphora, mydriasis followed by miosis, corneal herniation, hypopyon, ptosis, and anterior synechia developed in three of the animals.
Insights
High doses of BA6650, a fluoremethane-sulfonanilide sympathomimetic agent, caused ocular lesions and decreased intraocular pressure in Beagle dogs during a preclinical safety study.
Area of Science:
- Veterinary Ophthalmology
- Preclinical Toxicology
- Pharmacology
Background:
- Preclinical safety evaluations are crucial for assessing the potential adverse effects of new pharmaceutical agents.
- Sympathomimetic agents can influence various physiological processes, including ocular parameters.
Purpose of the Study:
- To evaluate the ocular safety of BA6650, an experimental fluoremethane-sulfonanilide sympathomimetic agent, in Beagle dogs.
- To determine the dose-dependent effects of BA6650 on intraocular pressure and ocular tissues.
Main Methods:
- A 14-day preclinical safety study involving Beagle dogs administered escalating oral doses of BA6650.
- Monitoring of intraocular pressure and daily clinical observations for ocular adverse effects.
- Histopathological examination of ocular tissues post-treatment.
Main Results:
- Three out of four dogs treated with BA6650 developed significant ocular lesions, including conjunctival hyperemia, corneal opacities, and hypopyon.
- A notable decrease in intraocular pressure was observed in treated dogs, from a mean of 17 mmHg to 8 mmHg.
- Untreated control dogs exhibited stable intraocular pressure within the 17-22 mmHg range.
Conclusions:
- BA6650, at high doses, induces severe ocular toxicity in Beagle dogs.
- The observed decrease in intraocular pressure may be associated with the sympathomimetic properties of BA6650 and warrants further investigation.
- These findings highlight potential risks associated with BA6650 administration and necessitate careful consideration in further drug development.