Toxicidade ambiental do ingrediente ativo farmacêutico nevirapina e de um medicamento à base de nevirapina.

Abstract

Nevirapine (NVP) is an active pharmaceutical ingredient (API) used in drugs for the treatment of human immunodeficiency virus infection, preventing its multiplication. It acts on the deoxyribonucleic acid transcription pathway in humans, inhibiting the reverse transcriptase enzyme. The chemical characteristics of NVP allow its accumulation in water and sediments and, for this reason, it may induce effects on other environmentally exposed species. The literature reports that the toxic effects of APIs can change when they are associated with excipients. In this sense, this study was unprecedented in assessing the toxicity of API and a drug based on NVP for the aquatic organisms Chlorella vulgaris, Artemia salina and Aliivibrio fischeri and for the plant Allium cepa. Aquatic toxicity was evaluated based on the effective concentration (EC) of 50% and 10%, determined by the log-logistic dose-response model for non-parametric data, in the free software R. It was observed that the growth of C. vulgaris was inhibited by the IFA and the drug, but their EC50% were not statistically different, suggesting that the excipients did not interfere with the growth inhibition of this species. On the other hand, IFA caused mortality (immobility) of A. salina nauplii, but no effect was observed for the drug. As for the A. fischeri species, it was observed that in the presence of excipients the EC50% of bioluminescence inhibition was lower than that observed for the API. The cytogenetic toxicity for NVP for the plant A. cepa was evaluated, for the first time, using the seeds as a model. This model made it possible to evaluate the unprecedented germination index (GI) and mutagenicity index (IMT). The GIs of seeds exposed to concentrations of 6.42 ± 0.58 and 9.54 ± 0.87 mg/L of API and 11.20 ± 1.13 mg/L of NVP-based medicine were statistically higher than the control negative (CN) and similar to the alkylating methylmethanesulfonate (MMS). About 10% inhibition of germination was observed at the concentration of 5.48 ± 0.44 mg/L of the drug and IGs similar to the negative control in the other concentrations. At all drug and API concentrations, the CR was statistically lower than the negative control, except for the 6.42 ± 0.58 mg/L API concentration, which was similar to the CN. At the concentration of 17.68 ± 1.29 mg/L of the NVP-based drug, the mitotic index (MI) was statistically higher than the negative control and similar to the MMS, indicating cytotoxicity. Chromosomal adherence was the most frequent chromosomal aberration in all groups exposed to NVP. The chromosomal abnormality indexes (CAIs) were statistically higher than the negative control, suggesting genotoxicity for all tested concentrations. The IMTs in the three API concentrations and in 17.68 ± 1.29 mg/L of the drug were statistically higher than the negative control, suggesting the possibility of mutagenicity. Finally, EC50% and cytogenetic effects indicate that NVP residues are of environmental interest and, in this sense, it can be concluded that reducing the presence of this micropollutant is an important factor to mitigate possible damage to other species. This study demonstrated the possibility of monitoring effluents in the routine of the pharmaceutical industry and, in this sense, preventing risks arising from exposure to drug residues for human health and the environment.