I am using Chloroquine and its effect on autophagy and I want to treat my cell culture with a dose close to the exposition with CQ treatment. So how valid is to use the mean serum concentration? or there is a model to adapt this value?
Dear Emerson.
You can treat your cell culture with any drug you wish. You just have to calculate the optimum concentratin. For your cell line according your experimental design.
Dear Emerson,
In a first estimation you could use an incubation concentration corresponding to average concentration in serum to be in the relevant range. Given the long half-life of chloroquine the serum concentration must be stable enough to make it directly relevant. It's better to actually use a range of concentration in vitro to establish a concentration-effect relationship and then relate to the concentrations seen in vivo.
When doing these comparisons, in general, one should consider binding. Only free unbound drug is expected to drive effects, so one needs to set conditions to match unbound drug concentrations, considering serum binding / plasma protein binding and binding to incubation medium. Chloriquine is a low binding compound, so this may not be a main factor in that particular case. However, chloroquine has high affinity for tissues / cellular material, so you should consider measuring concentrations in your test medium during incubation with cells, to make sure you match effective concentrations rather than nominal one, in case accumulation in cells impacts medium concentrations.
The aim is to match free concentrations at the site of action between systems. Here we assume that similar free concentration in serum and extracellular fluid leads to similar free concentrations in the relevant intracellular organelles.
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