Local irritation study of repeated lumbar intrathecal injection of Ziconotide Acetate / 药物评价研究

ABSTRACT

Objective To study the local irritation of repeated intrathecal injection of Ziconotide Acetate,and to provide reference for irritancy evaluation ofintrathecal injection.Methods Sixteen New Zealand rabbits were assigned into two groupsat randomControl group and Ziconotide Acetate group,eight animals each group.Totally 50 μL saline or Ziconotide Acetate (100 μg/mL) were administrated by repeated lumbar intrathecal injection once daily for 7 d.Animal behavior was observed every day,and four animals in each group were sacrificed 2 d later after the last injection,the lumbar spinal cord was removed for histopathological examination and irritancy evaluation.The remaining animals were sacrificed for initancy evaluation 14 d later after the last injection.Results Only one animal died after anesthesia on day three in saline group,while no obvious adverse reactions were observed in other rabbits during the entire study,and no intrathecal irritant reactions of histopathological examination were found in both groups.The reversible minor mechanical damage was observed at the injection point,2 d after the last administration.Conclusion For 7 d repeated lumbar intrathecal injection in rabbits,no intrathecal irritant reactions observed in Ziconotide group,and the New Zealand rabbit could be used as a local irritation evaluation model.