Safety and toxicological profile of the new antitussive levodropropizine.
Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), a new antitussive drug, was submitted to toxicological studies. Acute toxicity, both oral and intraperitoneal, in rats and mice and oral toxicity in guinea-pigs was low. Subchronic and chronic toxicity studies were performed in rats and dogs. For both species the maximum tolerated oral dosage was 24 mg/kg/d. Dose-related clinical signs were observed, consisting mainly in salivation in rats and sedation, peripheral vasodilatation and increased heart rate in dogs. Liver toxicity was found in both species at higher dosages. In rats, food intake and body weight gain were reduced. There were no effects on fertility, nor any teratogenic effects. Foetal and peri- and post-natal toxic effects were observed in rats only at 150 mg/kg/d. A set of mutagenicity tests yielded negative results. Therefore, levodropropizine is safe up to dosages 10 times greater than the one intended for clinical use and only slight adverse reactions were recorded at a dosage 30 times greater.
Bestetti
A
A
Research & Development Laboratories, Dompe' Farmaceutici S.p.A., Milan, Italy.
Giuliani
P
P
Nunziata
A
A
Melillo
G
G
Tonon
G C
GC
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000996:Antitussive Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005313:Fetal Death / Q000139:chemically induced; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D011247:Pregnancy; D011409:Propylene Glycols / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000996:Antitussive Agents; D011409:Propylene Glycols; C035916:dipropizine