Category Archives: Drug action

Arrhythmic risk: regression, single cell biophysics, or big tissue simulations?

On the 15th March I presented at an FDA public Advisory Committee hearing on the proposals of the CiPA initative. CiPA aims to replace the current testing for increased drug-induced Torsade de Pointes (TdP) arrhythmic risk, which is a human … Continue reading

Posted in Action Potential Models, Drug action, Future developments, Model Development, Safety Pharmacology, Tissue Simulations | Tagged , , , , , , , | 1 Comment

Uncertainty quantification for ion channel screening and risk prediction

This post accompanies our new paper in Wellcome Open Research. Regular readers of this blog will know that I worry about uncertainty in the numbers we are using to model drug action on electrophysiology quite a lot – see our … Continue reading

Posted in Drug action, Model Development, Safety Pharmacology, Stats and Inference | Tagged , , , , , , , , , | 4 Comments

Should I work with IC50s or pIC50s?

When you are expressing how much a drug inhibits something, it’s common to fit a Hill curve through a graph of concentration against % inhibition as shown here: In our case this is often ‘% inhibition’ for a given ionic … Continue reading

Posted in Drug action, Safety Pharmacology, Stats and Inference | Tagged , , , , , , , , , , , , | 1 Comment

Are 30 compounds enough to test our simulations?

I’ve just contributed to a new review ‘Recent developments in using mechanistic cardiac modelling for drug safety evaluation’, which discusses where we are with using mathematical models of the electrical activity of cardiac muscle cells to predict whether new drugs … Continue reading

Posted in Action Potential Models, Drug action, Ion Channel Models, Safety Pharmacology, Stats and Inference | Tagged , , , , | 7 Comments

Triangles and Conductances

Just a little post on something that’s really simple, not new, and might seem obvious to some people – but might help when choosing how to explore the effect of altering parameters on action potential model behaviour. The reason I … Continue reading

Posted in Action Potential Models, Drug action | Tagged , , , , , , | Leave a comment

In-silico Action Potential Prediction Web Portal

This post is to announce that we are making our in-silico action potential prediction web portal (AP-predict) available for public use. The portal is free, you just need to register for an account. We’d be happy to have any feedback on … Continue reading

Posted in Action Potential Models, Drug action, Safety Pharmacology | Tagged , , , , , , , | Leave a comment

Initial conditions and steady states

Today I came across a good (or bad, depending on how you look at it) example of initial conditions / steady-states having a massive effect on model behaviour. I think it is generally a good idea to get a model … Continue reading

Posted in Action Potential Models, Drug action, Numerics, Virtual Experiments | Tagged , , , , , , , | 2 Comments