Is it not important to incorporate the knowledge on PK/PD when studying bacterial killing kinetics?

Many researchers studying bacterial killing by antibiotics use single culture conditions as indicated in the earlier blogs. However, such conditions do not take into account of

1. variable drug levels that occur under in vivo conditions

2. protein binding. In in vitro conditions, drug is available as free drug whereas in in vivo conditions, drugs can be bound to proteins. Only the unbound drug is pharmacologically effective and relevant in predicting therapeutic efficacy

3. concentration of drug at target sites- the drug penetration into the target sites can be influenced by a number of factors which are absent in in vitro conditions

4. tissue distribution- depending on the extent of binding of drug molecules to tissue proteins, the concentration of unbound (free) drug can vary

5. importance of immune cells

6. the role of inoculum effect, paradoxical effect etc. (discussed earlier)

Because of these disadvantages, MIC or MBC or MBC₁₀₀ can not be considered as ideal pharmacodynamic parameters. They can only give approximate information about the effect of antibiotics.

Is it a good practice to extrapolate the results of single culture conditions as such to in vivo situations?