Related Experiment Videos
Toxicological studies of plafibride. Part 1: Acute toxicity and its determination after several administrations of
Abstract:
Acute toxicity studies of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) were carried out in mouse, rat, guinea pig and hamster by different administration routes. The effect of pretreatment with plafibride on acute toxicity was also studied for several days. Plafibride had low toxicity. Its LD50 p.o. was about 4000 mg/kg in rat, mouse and hamster. The LD50 i.p. was between 760 (673-859) mg/kg in NMRI mouse and 1050 (830-1328) mg/Kg in hamster. The LD50 i.v. was similar for rat and mouse (about 100 mg/kg). Pretreatment with plafibride did not alter acute toxicity, which implies the absence of accumulation of the compound which would have led to an increase in toxicity. Nor was there any appearance of enzymatic induction, in which case a decrease would be observed in the toxicity of the product.
Insights
Plafibride (ITA 104) exhibits low acute toxicity across multiple animal models and administration routes. Pretreatment studies indicate no accumulation or enzymatic induction, suggesting a favorable safety profile for this compound.
Area of Science:
- Pharmacology
- Toxicology
- Drug Safety
Background:
- N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea, also known as plafibride (ITA 104), is a compound requiring comprehensive safety evaluation.
- Understanding the acute toxicity profile is crucial for assessing the potential risks associated with plafibride.
- Investigating the effects of repeated administration and potential metabolic interactions is essential for drug development.
Purpose of the Study:
- To determine the acute toxicity of plafibride (ITA 104) in various animal species.
- To evaluate the impact of plafibride pretreatment on acute toxicity.
- To assess potential mechanisms influencing toxicity, such as accumulation or enzymatic induction.
Main Methods:
- Acute toxicity testing in mice, rats, guinea pigs, and hamsters.
- Administration of plafibride via oral (p.o.), intraperitoneal (i.p.), and intravenous (i.v.) routes.
- Pretreatment studies involving daily administration of plafibride over several days.
Main Results:
- Plafibride demonstrated low acute toxicity, with oral LD50 values around 4000 mg/kg in rats, mice, and hamsters.
- Intraperitoneal LD50 ranged from 760 mg/kg in mice to 1050 mg/kg in hamsters.
- Intravenous LD50 was approximately 100 mg/kg in rats and mice.
- Pretreatment with plafibride did not alter acute toxicity, indicating no significant accumulation or induction of enzymatic activity.
Conclusions:
- Plafibride (ITA 104) possesses a low acute toxicity profile across tested species and administration routes.
- The absence of altered toxicity upon pretreatment suggests no significant compound accumulation or adverse metabolic interactions.
- These findings support a favorable initial safety assessment for plafibride.