Toxicology Department, Sandoz Development Center,Lek Pharmaceuticals d.d., Ljubljana, Slovenia.
Drug Chem Toxicol. 2013 Jul;36(3):263-9. doi: 10.3109/01480545.2012.710628. Epub 2012 Sep 6.
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.
在单次静脉（i.v.）给药后，研究了胺碘酮 Lek 制剂（测试制剂）的毒性。与参比制剂 Cordarone（Cordarone（®）；惠氏制药公司，宾夕法尼亚州科利维尔，美国）相比，雌性小鼠静脉注射后的中位致死剂量（LD（50））为 294.0mg/kg 体重（b.w.），用于测试制剂和 227.5mg/kg b.w.用于 Cordarone。在雌性大鼠静脉注射后，测试制剂的 LD（50）值为 269.9mg/kg b.w.，Cordarone 为 192.4mg/kg b.w.。通过改变 Lek 制剂中胺碘酮的粒径，我们能够提高胺碘酮的溶解度，从而减少制备静脉注射制剂所需的赋形剂的数量和数量，因此，降低了本研究中观察到的急性毒性作用。
