Hattori H, Yamaguchi F, Wagai N, Kato M, Nomura M
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Toxicology. 1997 Nov 21;123(1-2):149-60. doi: 10.1016/s0300-483x(97)00118-2.
Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight beta-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.
过敏反应是人类常见的不良反应之一。然而，人们普遍认为，实际上没有可靠的动物模型可用于低分子量药物临床前测试以预测此类反应。本研究旨在比较八种β-内酰胺抗生素抗原潜力测试方法的检测能力，这些抗生素在人类中已报告有过敏结果。测试包括主动全身过敏反应（ASA）、迟发型皮肤反应（DSR）、用弗氏完全佐剂乳化的抗生素致敏豚鼠的最大化试验（GPMT）、被动皮肤过敏反应（PCA）以及作为血清学检测的酶联免疫吸附测定（ELISA）。PCA和ELISA虽然使用蛋白质偶联物作为检测抗原，尤其是ELISA，显示出相对较高发生率的阳性反应。另一方面，尽管在致敏和激发阶段仅使用抗生素，但GPMT是检测抗生素抗原潜力最敏感的方法。建议GPMT可被视为临床前测试中最可靠的方法。
