Acute and Subchronic Toxicity of Erdosten Ambroxol Hydrochloride Mixture by Gavage in Beagle Dogs

doi:10.19803/j.1672-8629.2021.01.05

Abstract

Abstract: Objective To observe the acute and subchronic toxicity after oral administration of erdostatin hydrochloride ambroxol mixture in Beagle dogs,and to provide reference for clinical safe dose design and toxicity monitoring.Methods Beagle dogs were selected for acute and 13-week subchronic toxicity tests.During the acute experiment,dogs were divided into erdostine hydrochloride ambromine mixture dose group (5.04 g/kg),erdostine hydrochloride group (4.80 g/kg),ambroxol hydrochloride group (0.24 g/kg) and blank control group using the maximum dose method.In the subchronic toxicity test,dogs were assigned to the high dose group (180 mg/kg),medium dose group (60mg/kg) and low dose group (20 mg/kg) of erdostine hydrochloride ambroxol mixture,while erdostine hydrochloride (171.4 mg/kg) group,ambroxol hydrochloride (8.6 mg/kg) group and blank control were also set up.The drug was given for thirteen consecutive weeks before the general condition,biochemical indexes and histopathology of the animals were examined.Results The results of acute toxicity tests showed that the main toxic reactions of animals were proneness,lethargy,tremor,inactivity and fatigue at a single dose (5.04 g/kg) of erdostatin hydrochloride ambroxol mixture,but these animals basically returned to normal on the second day,and the post-drug toxicity was similar to that of erdostine group and ambroxol hydrochloride group.The subchronic toxicity tests showed that at the end of administration and recovery,the levels of creatinine slightly increased in high dose group of erdostine hydrochloride ambroxol mixture and erdostine group,but no abnormality was found in the other groups.Conclusion The maximum dose of erdostatin hydrochloride ambroxol mixture was 5.04 g/kg in beagle dogs.Compared with erdosten (4.80 g/kg) and ambroxol hydrochloride (0.24 g/kg),the toxicity of the mixture group did not increase.The results of 13-week repeated administration of erdosten ambroxol hydrochloride mixture in beagle dogs showed that the middle dose (60 mg/kg)group had no observed adverse toxic reactions.This study may provide reference for clinical application of erdosten ambroxol hydrochloride mixture.

Key words: beagle dogs, erdostatin, ambroxol, oral, acute toxicity, subchronic toxicity

CLC Number:

R969.2

WANG Shuting, LI Hui, WANG Jiangxue, ZHANG Zixuan, MU Wenbo, GUO Xinmiao, YE Xiangfeng, JIN Hongtao. Acute and Subchronic Toxicity of Erdosten Ambroxol Hydrochloride Mixture by Gavage in Beagle Dogs[J]. Chinese Journal of Pharmacovigilance, 2021, 18(1): 24-29.

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