Abstract:

Objective    To assess the drug safety of ranolazine by studying its genotoxicity. Methods    The Ames test, micronucleus test of mice bone marrow polychromatic erythrocytes and sperm shape abnormality test were used to assess the genotoxicity of ranolazine. The Ames test included the methods of direct measurement and metabolism activation. The strains used in the Ames test were salmonella typhimurium histidine-deficient strain TA97， TA98， TA100 and TA102. Six treatment groups of ranolazine (5000, 2500, 1000, 500, 250 and 125μg/plate) were used during the study, and reverse mutational and positive control groups were set at the same time. There were 3 different administration groups with 222, 111 and 55mg/kg ranolazine, a negative control group (Veh) as well as positive control groups (40mg/kg) in the micronucleus test of mice bone marrow polychromatic erythrocytes and sperm shape abnormality test assay. Results    Compared with the control group, no statistical difference（P>0.05）in the number of colonies with back mutation per vessel in TA97,TA98,TA100 and TA102 strains treated with ranolazine at≤5000μg/plate with or without S9 activation was found. No dosagedependent relation was found. Moreover, within the dosage of 55-222mg/kg, both the induced micronuclei of mice bone marrow polychromatic erythrocytes and the sperm shape abnormality rate showed no statistical difference（P＞0.05）between ranolazine treated and control groups in mice. Conclusion    Ranolazine does not show its genetic toxicity within the dose range that was measured.

Key words:  Ranolazine； Ames test； Micronucleus； Sperm abnormality； Genotoxicity； Mice