title: Reduced intravenous toxicity of amiodarone nanosuspension in mice and rats.
abstract: The toxicity of amiodarone Lek formulation (test formulation) was investigated after a single intravenous (i.v.) administration to mice and rats. When compared to the reference item, Cordarone (Cordarone(®); Wyeth Pharmaceuticals Inc., Collegeville, Pennsylvania, USA), median lethal dose (LD(50)) after i.v. administration in female mice was 294.0 mg/kg body weight (b.w.) for the test formulation and 227.5 mg/kg b.w. for Cordarone. In female rats after i.v. administration, the LD(50) value was 269.9 mg/kg b.w. for the test formulation and 192.4 mg/kg b.w. for Cordarone. By altering the particle size of amiodarone in the Lek formulation, we were able to improve the solubility of amiodarone, thereby decreasing the number and quantity of excipients needed for preparation of the i.v. formulation and, consequently, reduced the acute toxic effects observed in the present study.
authors.affiliation: Toxicology Department, Sandoz Development Center,Lek Pharmaceuticals d.d., Ljubljana, Slovenia. ester.lovsin_barle@novartis.com
authors.forename: Ester Lovšin
authors.initials: EL
authors.lastname: Barle
authors.forename: Manica
authors.initials: M
authors.lastname: Cerne
authors.forename: Luka
authors.initials: L
authors.lastname: Peternel
authors.forename: Miha
authors.initials: M
authors.lastname: Homar
mesh_terms: D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000633:toxicity; D005260:Female; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions; D018675:Toxicity Tests
chemical_list: D000889:Anti-Arrhythmia Agents; D005079:Excipients; D013535:Suspensions; D000638:Amiodarone