Nur fatmawati
16611047
The comprehensive in vitro proarrhythmia assay ( CiPA) initiative- update on progress.
The
Comprehensive in vitro Proarrhythmia Assay (CiPA) was proposed
to improve prediction of TdP risk, using in silico models
and in vitro multi-channel pharmacology data as integral parts
of this initiative. Previously, Combining dynamic interactions between drugs
and the rapid delayed rectifier potassium current (IKr) with multi-channel
pharmacology is important for TdP risk classification, and we modified the
original O'Hara Rudy ventricular cell mathematical model to include a Markov
model of IKr to represent dynamic drug-IKr interactions (IKr-dynamic ORd
model). A novel metric that could separate drugs with different TdP liabilities
at high concentrations based on total electronic charge carried by the major
inward ionic currents during the action potential. Using this optimized model
and manual patch clamp data, developed an updated version of the metric that
quantifies the net electronic charge carried by major inward and outward ionic
currents during the steady state action potential, which could classify the
level of drug-induced TdP risk across a wide range of concentrations and pacing
rates.
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