The numerical probability of carcinogenicity to humans of some pharmaceutical drugs: Alkylating agents, topoisomerase inhibitors or poisons, and DNA intercalators.
| Autor: | Suarez-Torres JD; Department of Pharmacy, Faculty of Sciences, Universidad Nacional de Colombia, Bogotá, Colombia.; Department of Toxicology, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.; Faculty of Pharmacy, Institute of Pharmaceutical Research, Universidad Central de Venezuela, Caracas, Venezuela., Orozco CA; Department of Animal Health, Faculty of Veterinary Medicine and Zootechnics, Universidad Nacional de Colombia, Bogotá, Colombia., Ciangherotti CE; Faculty of Pharmacy, Institute of Pharmaceutical Research, Universidad Central de Venezuela, Caracas, Venezuela. |
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| Jazyk: | angličtina |
| Zdroj: | Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2021 Dec; Vol. 35 (6), pp. 1069-1089. Date of Electronic Publication: 2021 Apr 27. |
| DOI: | 10.1111/fcp.12674 |
| Abstrakt: | The nonclinical branch of regulatory pharmacology has traditionally relied on the sensitivity and specificity of regulatorily recommended bioassays. Nonetheless, any predictive testing (eg, safety pharmacology) with less than 100% sensitivity or 100% specificity is prone to deliver false positive or negative results (namely, outcomes discordant to the clinical gold standard). It was recently suggested that the statistics-based and regulatory pertinent "predictive values approach" (PVA) might help to reach a more predictive use of preclinical testing data. To resolve the associated probability of carcinogenicity to humans, the PVA was applied to 37 pharmaceuticals bearing inadequate epidemiological evidence of carcinogenicity, but identifiable as unequivocal mutagens. According to current knowledge, a 98.9% (or more) probability of carcinogenicity to humans was reckoned for those 37 genotoxic drugs. Accordingly, these pharmaceutical drugs might be either scientifically or regulatorily regarded as "carcinogenic to humans." In the USA, European Union, or Canada as examples, the great majority of these 37 pharmaceuticals are authorized for medical use in humans. From the results of the present appraisal, the following is suggested (1) for the pharmaceuticals listed in this report, to include significant carcinogenicity warnings in their prescribing information; (2) to conduct pharmacoepidemiology studies or risk-benefit analyses (if warranted), and (3) based on the respective risk-benefit analyses, to re-evaluate the authorization of hydralazine and phenoxybenzamine as antihypertensives, oxcarbazepine as an anticonvulsant, and phenazopyridine as a urinary tract antimicrobial or analgesic. For the four latter drugs (eg, phenoxybenzamine), a 99.5% probability of carcinogenicity to humans was estimated. (© 2021 Société Française de Pharmacologie et de Thérapeutique.) |
| Databáze: | MEDLINE |
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