Gray J E
Fundam Appl Toxicol. 1981 May-Jun;1(3):290-2. doi: 10.1016/s0272-0590(81)80131-5.
Musculoirritancy testing in the rabbit has been recognized as sufficiently sensitive to be highly predictive of human tolerance for intramuscularly administered drugs. A three-part study consisting of gross characterization of the lesion, microscopic observation and determination of serum activity of the enzyme creatine phosphokinase (CPK) has evolved as a standard test for evaluating single injection injury in the muscle. Injection and tissue processing procedures are described as well as a revised grading system for gross examination based on degrees of necrosis and hemorrhage, respectively. Based on 213 determinations, the control mean serum CPK activity was 262 +/- 113 I.U./liter. The importance of pretest acclimation of rabbits in establishing this value was emphasized. Designations of slight, moderate, or marked irritation are based on accumulative scoring of all rabbits at postinjection intervals of 1, 3, and 7 days. At 24 hr postinjection, serum CPK activities up to and including a range of 2000-3000 I.U./liter have been shown to be compatible with slight irritation and are considered predictive of human tolerance.
家兔的肌肉刺激性试验已被认为具有足够的敏感性，能够高度预测人体对肌肉注射药物的耐受性。一项由病变大体特征描述、显微镜观察以及肌酸磷酸激酶（CPK）血清活性测定三部分组成的研究，已发展成为评估肌肉单次注射损伤的标准试验。文中描述了注射和组织处理程序，以及基于坏死和出血程度的大体检查修订分级系统。基于213次测定，对照血清CPK活性均值为262±113国际单位/升。强调了家兔预试验适应性在确定该值中的重要性。轻度、中度或重度刺激的判定基于在注射后1天、3天和7天的间隔时间对所有家兔的累积评分。注射后24小时，血清CPK活性高达2000 - 3000国际单位/升（包括该范围）已被证明与轻度刺激相符，并被认为可预测人体耐受性。
