Studies on genotoxicity and carcinogenicity of antibacterial, antiviral, antimalarial and antifungal drugs.
This review provides a compendium of retrievable results of genotoxicity and animal carcinogenicity studies performed of antibacterial, antiviral, antimalarial and antifungal drugs of long-term or intermittent frequent use. Of the 48 drugs considered, 9 (18.75%) do not have retrievable data, whereas the other 39 (81.25%) have at least one genotoxicity or carcinogenicity tests result. Of these 39 drugs, 24 tested positive in at least one genotoxicity assay and 19 in at least one carcinogenicity assay; 14 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 results of long-term carcinogenesis assays, of 23 drugs with both genotoxicity and carcinogenicity data: 2 (8.7%) were neither genotoxic nor carcinogenic, 2 (8.7%) tested positive in at least one genotoxicity assay but were non-carcinogenic, 4 (17.4%) tested negative in genotoxicity assays but were carcinogenic, and 15 (65.2%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 18 (37.5%) of the 48 drugs examined had all data required by present guidelines for testing of pharmaceuticals, but a fraction of them (49%) were developed and marketed prior to the present regulatory climate. In the absence of compelling indications, the prescription of the 19 drugs that are animal carcinogens should be avoided.
Department of Internal Medicine, Division of Clinical Pharmacology and Toxicology, University of Genoa, Viale Benedetto XV, 2, I-16132 Genoa, Italy.
Giovanni
G
Brambilla
Francesca
F
Mattioli
Luigi
L
Robbiano
Antonietta
A
Martelli
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000935:Antifungal Agents / Q000633:toxicity*; D000962:Antimalarials / Q000633:toxicity*; D000998:Antiviral Agents / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D009153:Mutagens / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000962:Antimalarials; D000998:Antiviral Agents; D002273:Carcinogens; D009153:Mutagens