Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Genoa, Italy.
Mutagenesis. 2010 Jul;25(4):315-26. doi: 10.1093/mutage/geq025. Epub 2010 May 17.
This review provides a compendium of retrievable results of genotoxicity and carcinogenicity assays performed on marketed gastrointestinal drugs. Of the 71 drugs considered, 38 (53.5%) do not have retrievable data, whereas the other 33 (46.5%) have at least one genotoxicity or carcinogenicity test result. Of these 33 drugs, 15 tested positive in at least one genotoxicity assay and 13 in at least one carcinogenicity assay; 8 of them gave a positive response in both at least one genotoxicity assay and at least one carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, of 21 drugs with both genotoxicity and carcinogenicity data: 6 (28.6%) are neither genotoxic nor carcinogenic, 2 (9.5%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 5 (23.8%) tested negative in genotoxicity assays but were carcinogenic and 8 (38.1%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 12 (16.9%) of the 71 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior the present regulatory climate.
这篇综述提供了已上市胃肠道药物的遗传毒性和致癌性检测的可检索结果摘要。在所考虑的 71 种药物中，有 38 种（53.5%）没有可检索的数据，而其他 33 种（46.5%）至少有一项遗传毒性或致癌性测试结果。在这 33 种药物中，有 15 种在至少一项遗传毒性检测中呈阳性，有 13 种在至少一项致癌性检测中呈阳性；其中 8 种在至少一项遗传毒性检测和至少一项致癌性检测中均呈阳性反应。关于遗传毒理学发现对长期致癌性检测结果的预测性，在有遗传毒性和致癌性数据的 21 种药物中：6 种（28.6%）既非遗传毒性也非致癌性，2 种（9.5%）至少在一项遗传毒性检测中呈阳性但非致癌性，5 种（23.8%）在遗传毒性检测中呈阴性但致癌性，8 种（38.1%）在至少一项遗传毒性检测和至少一项致癌性检测中呈阳性反应。在所检查的 71 种药物中，仅有 12 种（16.9%）具有目前药物测试指南所需的所有数据，但其中很大一部分是在当前监管环境之前开发和上市的。
