摘要
目的通过比较不同的校正公式来确定适合清醒Beagle犬QT间期校正的公式,以用于非临床安全药理学研究。方法用12只已进行遥测植入的Beagle犬(雌、雄各半)连续采集至少24 h的心电图数据,测量并分析该期间内动物的RR和QT间期,采用8种校正公式(QTcF、QTcB、QTcHDG、QTcV、QTcFRM、QTcNAK、QTcI、QTca)计算QTc,然后对不同校正公式计算的QTc与RR进行线性回归分析,寻找R值最接近零和P值最大的校正公式,并进行性别间的差异比较。结果使用8种校正公式计算的QTc比较显示,QTca个体校正公式校正的R值为-0.025,P值为0.679;QTcI校正的R值为-0.040,P值为0.501;QTcF校正的R值为0.044,P值为0.461。与其他公式相比QTca校正公式的R值最接近于零并且P值最高,表明QTca计算的QTc受RR的影响程度最小,且表明QTc与RR 2个变量之间无显著相关性。在雄性Beagle犬中,通过QTcI个体校正公式校正的R值为0.070,P值为0.401;其次是QTca,R值为0.072,P值为0.391;再者为QTcF,R值为0.118,P值为0.159。在雌性Beagle犬中,通过QTcF通用校正公式校正的R值为-0.026,P值为0.755;其次是QTca,R值为-0.135,P值为0.108。雄性和雌性Beagle犬之间通过与其他公式的R值和P值的比较,表明QTca和QTcF校正公式计算的QTc都受RR影响程度较小且表明QTc与RR 2个变量之间无显著相关性。结论在本机构试验条件下,使用个体校正公式QTca更适合校正清醒无束缚条件下Beagle犬的QT间期,可作为安全药理学研究中的优选方式。
Objectives The correction formulas suitable for QT interval correction in conscious Beagle dogs are determined by comparing different correction formulas in non-clinical safety pharmacology study.Methods 12 Beagle dogs(half male and half female)with existing telemetry implants are used to continuously collect ECG data for at least 24 hours,and the RR and QT intervals of the animals during the analysis period were measured and analyzed.QTc was calculated using eight correction formulas(QTcF,QTcB,QTcHDG,QTeV,QTcFRM,QTcNAK,QTcl,QTca),comand then linear regression analysis was performed on QTc calculated by different correction formulas and RR,searching for thecorrectionformulas with R value closest to zero and P value maximum,and comparing the differences between genders.Results The comparison of QTc calculated using eight correction formulas showed that R value corrected by QTca individual correction formula is-0.025 and P value is 0.679;R value corrected by QTcI is-0.040 and P value is 0.501;R value correctedby QTcF is 0.044 and P value is 0.461.The R value of the QTca-corrected formula is the closest to zero and the P value is the highest compared to the other formulas,indicating that QTca-calculated QTc was minimally affected by RR and indicating that there are no significant correlation between QTc and RR variables.In male Beagle dogs,R value by the individual correction formula for QTcI is 0.070,P value is 0.401;followed by QTca,R value is 0.072 and P value is 0.391;and furthermore,R value is 0.118 and P value is 0.159 for QTcF.In female Beagle dogs,R value by the universal correction formula for QTcF is-0.026,P value is 0.755;followed by QTca,R value is-0.135,P value is 0.108.Comparison of R and P values with other formulas between male and female Beagle dogs indicated that QTca and QTcF correction formula-calculated QTc were both less affected by RR and indicated no significant correlation between QTc and RR variables.Conclusion Under the experimental conditions in our institution,the effect on QT interval i
作者
王庚莉
曹竹杰
黄芯玉
王三龙
张素才
WANG Gengli;CAO Zhujie;HUANG Xinyu;WANG Sanlong;ZHANG Sucai(School of Public Health,Zhengzhou University,Zhengzhou 450066,China;JOINN Laboratories(China)Co.,Ltd.,Beijing 100176,China;National Institutes for Food and Drug Control,National Center of Safety Evaluation of Drug,Beijing Key Laboratory of Nonclinical SafetyEvaluationof Drugs,Beijing 100176,China)
出处
《药物评价研究》
CAS
北大核心
2024年第9期2075-2081,共7页
Drug Evaluation Research
