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

[摘要] References(13)Cited-By(4)Supplementary materials(1)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 inter-facility 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.

[学科分类] 药学

[关键词] facility variability;action potential assay;guinea-pig papillary muscle;QT PRODACT