A single-dose and 4-week repeat-dose toxicity and toxicokinetic study of pediatric Reduning injection in weaning Beagle dogs
SUN Zu-yue
LI Fang
ZHENG Chi-yang
CHEN Ding-shi
CHEN Li-fen
XU Li
YAN Han
WANG Zhong-hui
LI Lei
WANG Fen
ZHOU Li
Abstract：Objective:To study the potential toxicity of pediatric Reduning Injection(RDN)in weaning Beagle dogs(PND49),a study was conducted for a 4-week administration period and a single-dose via intravenous injection.This research aims to support subsequent clinical risk assessment for children.Methods:In a single-dose toxicity study,weaning Beagle dogs(PND49)were administrated for 30 mL stock solution per kg(78 g crude drug/kg)within 24 h following litter grouping.In a 4-week repeat-dose toxicity study,weaning Beagle dogs were administrated RDN(2.0,5.0 and 10.0 mL of stock solution kg·day-1)for clinical observation after Within-litter grouping,laboratory examination,autopsy and histopathology examination.And the toxicokinetics parameters such as Tmax,AUC and Cmax were calculated.Results:In the single-dose toxicity study,no significant toxic reaction was observed in the pediatric RDN.In the second study,signs related to amplification of pharmacological effects were observed only in weaning Beagle dogs in each dose group,and no significant signs of toxicity related to the test article were observed.All the examinations and parameters were normal.Furthermore,the process of exposure and elimination of pediatric RDN exhibited linear dynamic characteristics.Conclusion:The MTD of RDN exceeds 78 g crude drug/kg,while the NOAEL was 26.0 g crude drug/kg(It is 10 times the equivalent dose of dogs,20 times the clinical dose,and 33.3 times the pharmacodynamic dose).
Keywords：Reduning injectiontraditional Chinese medicine injectionspediatric medicationsweaning animal studyBeagle dogsafety assessment
Publication Date：2025-05-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：10( 1053-1062 )