Preclinical safety evaluation of Jinkui Shenqi pills

doi:10.19803/j.1672-8629.20220512

Abstract

Abstract: Objective To investigate the toxicity of Jinkui Shenqi pills after single administration and after 26 weeks of repeated administration so as to provide reference for safe clinical use. Methods ICR mice were given intragastrically the highest concentration and maximum dose of Jinkui Shenqi pills before the animal toxicity was observed 14 days after administration (11.2 g·kg^-1 BW, which was 102 times the clinical human dose). SD rats were randomly divided into the control group and Jinkui Shenqi pill high-dose, medium-dose and low-dose groups (5.6 g·kg^-1 BW, 2.8 g·kg^-1 BW, 1.4 g·kg^-1 BW, which were 51 times, 25.5 times, 12.75 times the clinical human dose, respectively), gavaged twice a day for 26 weeks. Thirteen weeks and 26 weeks into administration and during the four weeks of recovery, the body weight, food intake, hematology and coagulation indexes of the rats were detected by a blood analyzer, and the related biochemical indexes by an automatic biochemical analyzer. Histopathological examination was conducted to evaluate the potential toxicity, reversibility of toxicity, and possible secondary and/or delayed effects of the drug. Results After single-dose toxicity test and during the 14 days of observation, there was no abnormality or death among the rats. The maximum dose of administration (MFD) was 11.2 g·kg^-1 BW, which was equivalent to 102 times the clinical human dose. Twenty-six weeks of continuous intragastric administration of Jinkui Shenqi pills did not cause any serious adverse reactions among the SD rats. No histopathological changes related to drug toxicity were observed in major organs of the rats. There was no delayed drug toxicity after drug withdrawal. The NOAEL was 5.6 g·kg^-1 BW·d^-1, which was 51 times the clinical human dose. Conclusion Jinkui Shenqi pills cause neither acute toxic reactions nor potential/secondary/delayed toxic reaction after long-term administration. It is safe at the therapeutic doses.

Key words: Jinkui Shenqi pill, mice, rats, toxicity, single administration, repeated administration, safety

CLC Number:

R961
R994

ZUO Zeping, TIAN Yingying, XU Yi, JIANG Kewu, YANG Shuo, YANG Hairun, ZHANG Zhicong, CAO Xinyao, WU Xiaoru, WANG Zhibin. Preclinical safety evaluation of Jinkui Shenqi pills[J]. Chinese Journal of Pharmacovigilance, 2023, 20(7): 775-782.

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