Comparison of different QT correction formulas in safety pharmacology studies in conscious Beagle dogs
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,QTcV,QTcFRM,QTcNAK,QTcI,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 in conscious unrestrained Beagle dogs could be accurately corrected using the individual correction formula QTca which can be used as a preferred method in safety pharmacology study.
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