Can somebody help me to understand how can I translate a drug dosage used in cultured cells to that that should be used in humans. Does it depend in some way on the molecules I'm working with and how it's administered?
It's already quite complicated and unreliable for animal to human dose translation. Here is an example: http://www.ncbi.nlm.nih.gov/pubmed/17942826
But dose conversion from cells to human is not possible, I think. There are too many unknown factors if you don't know the pharmacokinetics in humans yet. On the other side of the equation you don't know the metabolic capacity of your cell line for your drug and how it compares to the situation in vivo. Therefore I would assume there are way too many unknown variables to make any reasonable assumptions.
It depends on several factors including what type of cell cultures you are using (animal vs. human). The seeding rate, the final volume of the culture medium. After finalizing this stage you move to the PK model stage where you need to consider the route of exposure and the various toxicokinetic parameters for your drug especially the absorption factor via the designated route of administration. Hope this helps.
I agree with Georg. Extrapolation (even if its done carefully based on pharmacokinetic data), may not be useful. This is because solvents (alcohol and DMSO) commonly used for dissolving drugs to add in cell culture, have their own toxicity. So, the maximum dose of a drug you can add to cells is highly dependent on its solubility in these solvents. In practical terms, you may not be able to add the maximal amount of drug suggested by the calculation from in vivo data. For lower concentrations, this may not be a problem. Hope this helps!
Cell line studies cannot be a basis for human dose , attempts will be futile. We should use this data for the purpose of safety and to explain the possible mechanism of action.
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Pharmaceuticals
- Drugs