QT PRODACT: Inter- and Intra-facility Variability of the Action Potential Assay Using Isolated Guinea-Pig Papillary Muscles

Abstract

Sixteen pharmaceutical companies and 6 contract research organizations in QT PRODACT acquired data on the action potentials in isolated guinea-pig papillary muscles using a standard protocol established by the QT PRODACT. Inter- and intra-facility variability for each of the parameters in the pre-application values and Δ% change after vehicle (0.1% DMSO) or dl-sotalol (30 μmol/L) treatment were examined using a nested model. Inter-facility variability of each of the parameters in the pre-application values were Vmax > APDs = APD30–90 > APA = RMP (descending order). The inter-facility variability of all of the parameters was almost the same or was less as compared with the intra-facility variability. Inter-facility variability for the Δ% change for each parameter after dl-sotalol treatment showed a tendency similar to the results for the pre-application values. Comparing the inter- and the intra-facility variability, the interfacility variation did not exceed the intra-facility variation. All facilities found that dl-sotalol prolonged APD. Therefore, it is suggested that the test system using this standard protocol is useful as a non-clinical evaluation system for QT prolongation. Moreover, the results are considered to be directly comparable between multiple facilities.Supplementary material (Appendix): available only at http://dx.doi.org/10.1254/jphs.QT-B5. Keywords:: facility variability, action potential assay, guinea-pig papillary muscle, QT PRODACT