Brambilla Giovanni, Martelli Antonietta
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV 2, I-16132 Genoa, Italy.
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV 2, I-16132 Genoa, Italy.
Mutat Res. 2009 Mar-Jun;681(2-3):209-229. doi: 10.1016/j.mrrev.2008.09.002. Epub 2008 Sep 19.
This survey is a compendium of genotoxicity and carcinogenicity information of 838 marketed drugs, whose expected clinical use is continuous for at least 6 months or intermittent over an extended period of time. Of these 838 drugs, 366 (43.7%) do not have retrievable genotoxicity or carcinogenicity data. The remaining 472 (56.3%) have at least one genotoxicity or carcinogenicity test result. Of the 449 drugs with at least one genotoxicity test result, 183 (40.8%) have at least one positive finding. Of the 338 drugs with at least one carcinogenicity test result, 160 (47.3%) have at least one positive result. Concerning the predictivity of genetic toxicology findings for long-term carcinogenesis assays, of the 315 drugs which have both genotoxicity and carcinogenicity data 116 (36.8%) are neither genotoxic nor carcinogenic, 50 (15.9%) are non-carcinogens which test positive in at least one genotoxicity assay, 75 (23.8%) are carcinogenic in at least one sex of mice or rats but test negative in genotoxicity assays, and 74 (23.5%) are both genotoxic and carcinogenic. Only 208 (24.8%) of the 838 drugs considered have all data required by current guidelines for testing of pharmaceuticals. However, it should be noted that a large fraction of the drugs considered were developed and marketed prior to the present regulatory climate. Although the laws do not require re-testing based on revised standards, in the absence of epidemiological studies excluding a carcinogenic risk to humans, a re-evalutation would be appropriate.
本调查是838种已上市药物的遗传毒性和致癌性信息汇编，这些药物预期的临床使用为持续至少6个月或在较长时期内间歇性使用。在这838种药物中，366种（43.7%）没有可检索到的遗传毒性或致癌性数据。其余472种（56.3%）至少有一项遗传毒性或致癌性测试结果。在449种至少有一项遗传毒性测试结果的药物中，183种（40.8%）至少有一项阳性发现。在338种至少有一项致癌性测试结果的药物中，160种（47.3%）至少有一项阳性结果。关于遗传毒理学结果对长期致癌试验的预测性，在315种既有遗传毒性又有致癌性数据的药物中，116种（36.8%）既无遗传毒性也无致癌性，50种（15.9%）是非致癌物但在至少一项遗传毒性试验中呈阳性，75种（23.8%）在至少一种性别小鼠或大鼠中具有致癌性但在遗传毒性试验中呈阴性，74种（23.5%）既有遗传毒性又有致癌性。在考虑的838种药物中，只有208种（24.8%）具备现行药品测试指南要求的所有数据。然而，应当指出的是，所考虑的大部分药物是在当前监管环境之前研发和上市的。尽管法律不要求根据修订标准重新测试，但在没有排除对人类致癌风险的流行病学研究的情况下，进行重新评估是合适的。
