Mutagenicity of the new quinolone antibacterial agent levofloxacin

A new quinolone antibacterial agent (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10- (4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), was studied for mutagenicity using the following short-term in vitro and in vivo tests. 1.

reverse mutation test (Ames method) on S. typhimurium and E. coli; and HGPRT forward mutation test, cytogenetic test, and sister chromatid exchange (SCE) test, all on Chinese hamster cells. 2. In vivo studies: mouse micronucleus test, SCE test on mouse bone marrow cell, in vivo-in vitro unscheduled DNA synthesis (UDS) test on rat primary hepatocytes, and dominant lethal test in BDF1 mice. In the in vitro tests for SCE and for chromosomal aberration, DR-3355 gave dose-dependent positive responses, but no mutagenicity was observed in the same indicators of the in vivo studies, even at the maximum tolerated doses. This strongly suggested that DR-3355 would have no mutagenic effects when used in the treatment of infectious diseases. DR-3355 did not show any positive response in the reverse mutation test, the HGPRT mutation test, the in vivo-in vitro UDS test or the dominant lethal test. These results suggest that chemotherapy with DR-3355 should have no mutagenic effect in man.