Brazeau G A, Fung H L
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
Pharm Res. 1989 Feb;6(2):167-70. doi: 10.1023/a:1015940811827.
An isolated rat muscle preparation was developed to screen for muscle damage (myotoxic potential) following intramuscular injections. Myotoxicity is evaluated by the total cumulative efflux of the enzyme creatine kinase from the extensor digitorum longus muscle into the incubation medium over a 2-hr period or by the slope of the cumulative creatine kinase efflux curve. The system allows for rapid screening of compounds and/or formulations regarding their myotoxic potential and is not sensitive to fluctuations of in vivo creatine kinase levels caused by animal handling or patient conditions. A good rank-order correlation was obtained between this in vitro technique and the in vivo myotoxicity of a number of pharmaceutical formulations, as indicated by circulating creatine kinase levels and histological observations.
开发了一种分离的大鼠肌肉制剂，用于筛选肌肉注射后的肌肉损伤（肌毒性潜力）。通过在2小时内将肌酸激酶从趾长伸肌中释放到孵育培养基中的总累积量，或通过肌酸激酶累积释放曲线的斜率来评估肌毒性。该系统允许快速筛选化合物和/或制剂的肌毒性潜力，并且对动物处理或患者状况引起的体内肌酸激酶水平波动不敏感。如循环肌酸激酶水平和组织学观察所示，该体外技术与多种药物制剂的体内肌毒性之间获得了良好的等级相关性。
