PDF(Pubmed)
Abstract：
According to the ICH S3A Q&A, microsampling is applicable to pharmaceutical drugs and toxicological analysis. Few studies have reported the effect of microsampling on the toxicity of immunotoxicological drugs. The aim of this multicenter study was to evaluate the toxicological effects of serial microsampling on rats treated with azathioprine as a model drug with immunotoxic effects. Fifty microliters of blood were collected from the jugular vein of Sprague-Dawley rats at six time points from day 1 to 2 and 7 time points from day 27 to 28. The study was performed at three organizations independently. The microsampling effect on clinical signs, body weights, food consumption, hematological parameters, biochemical parameters, urinary parameters, organ weights, and tissue pathology was evaluated. Azathioprine-induced changes were observed in certain hematological and biochemical parameters and thymus weight and pathology. Microsampling produced minimal or no effects on almost all parameters; however, at 2 organizations, azathioprine-induced changes were apparently masked for two leukocytic, one coagulation, and two biochemical parameters. In conclusion, azathioprine toxicity could be assessed appropriately as overall profiles even with blood microsampling. However, microsampling may influence azathioprine-induced changes in certain parameters, especially leukocytic parameters, and its usage should be carefully considered.
摘要：
根据ICHS3A问答，微量采样适用于药物和毒理学分析。很少有研究报道微量采样对免疫毒理学药物毒性的影响。这项多中心研究的目的是评估连续微量采样对硫唑嘌呤作为具有免疫毒性作用的模型药物治疗的大鼠的毒理学作用。在第1天至第2天的6个时间点和第27天至第28天的7个时间点从Sprague-Dawley大鼠的颈静脉收集50微升血液。该研究在三个组织中独立进行。微量采样对临床体征的影响，体重,食物消费,血液学参数,生化参数，尿参数,器官重量,并进行组织病理学评价。观察硫唑嘌呤引起的某些血液学和生化参数以及胸腺重量和病理的变化。微量采样对几乎所有参数产生的影响最小或没有影响；然而，在两个组织中，硫唑嘌呤诱导的变化显然掩盖了两个白细胞，一次凝结,和两个生化参数。总之,硫唑嘌呤毒性可以适当地评估为总体概况，即使使用血液微量采样。然而,微量采样可能会影响硫唑嘌呤引起的某些参数的变化，尤其是白细胞参数，它的用法应该仔细考虑。
