QT PRODACT: inter- and intra-facility variability of the action potential assay using isolated guinea-pig papillary muscles.
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 Delta% change after vehicle (0.1% DMSO) or dl-sotalol (30 micromol/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 Delta% 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.
Japan Pharmaceutical Manufacturers Association (JPMA)/QT PRODACT, Tokyo, Japan. ryuzaburo.yamazaki@po.rd.taisho.co.jp
Ryuzaburo
R
Yamazaki
Masayuki
M
Yamada
Kazuo
K
Kobayashi
Shin-ichi
S
Kitani
Chiaki
C
Shimada
Takashi
T
Shimosato
Tatsuya
T
Mori
Hideki
H
Suganami
Keiji
K
Yamamoto
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001681:Biological Assay; D016208:Databases, Factual; D004121:Dimethyl Sulfoxide; D004345:Drug Industry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007753:Laboratories; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D015203:Reproducibility of Results; D013015:Sotalol / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D004121:Dimethyl Sulfoxide