Biological safety studies of gemifloxacin mesylate and related substances.
OBJECTIVE
The aim of this study was to evaluate the cytotoxic, phototoxic, genotoxic and photogenotoxic potential of gemifloxacin mesylate (GFM), its main synthetic impurity (SI) and one isolated and structurally elucidated degradation product (DP).


METHODS
The neutral red uptake (NRU) and reduction of 2,5-diphenyl-3,-(4,5-dimethyl-2-thiazolyl)tetrazolium bromide (MTT) assays were performed as in vitro endpoints to evaluate cytotoxicity and phototoxicity in a 3T3 cell line, and predict toxicity and/or phototoxicity after systemic administration of the drug. The in vitro alkaline single-cell electrophoresis (comet) assay was used to evaluate the genotoxic and photogenotoxic potential of the substances using the same cell line.


RESULTS
The results showed that the SI and the DP are more cytotoxic and phototoxic than the drug GFM using the 3T3 cell line. In the comet assay, the drug GFM was found to be more genotoxic and photogenotoxic than its related substances.


CONCLUSIONS
Our findings highlight the relevance of the biological safety studies to increase the knowledge regarding the toxic potential of the related substances, which can be associated with the drug side effects and toxicity.
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga 2752/402, 90610-000 Porto Alegre-RS, Brazil. csoldatelli30@hotmail.com
Clésio S
CS
Paim
Daniele R
DR
Nogueira
Montserrat
M
Mitjans
David
D
Ramos Lopez
Joaquin
J
de Lapuente Perez
Martin
M
Steppe
Elfrides E S
EE
Schapoval
María Pilar
MP
Vinardell
D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D024841:Fluoroquinolones / Q000737:chemistry* / Q000633:toxicity; D005562:Formazans / Q000737:chemistry; D000077735:Gemifloxacin; D051379:Mice; D009287:Naphthyridines / Q000737:chemistry* / Q000633:toxicity; D009499:Neutral Red / Q000737:chemistry; D010084:Oxidation-Reduction; D013778:Tetrazolium Salts / Q000737:chemistry; D014466:Ultraviolet Rays
D024841:Fluoroquinolones; D005562:Formazans; D009287:Naphthyridines; D013778:Tetrazolium Salts; C079782:MTT formazan; D009499:Neutral Red; D004247:DNA; D000077735:Gemifloxacin