# Which pKa should I use in this Henderson/Hasselbalch rearrangement?

I have a question about the following formula: $$Mu/Pu = \frac{1+10^{pHm - pKa}}{1+10^{pHp- pKa}}$$ This formula can be found in the following paper: Begg, E. J., & Atkinson, H. C. (1993). Modelling of the passage of drugs into milk. Pharmacology & Therapeutics, 59(3), 301–310. https://doi.org/10.1016/0163-7258(93)90072-l.

$$Mu/Pu$$ defines the ratio of an unbound drug between mother's milk $$Mu$$ and plasma $$Pu$$. $$pHm$$ and $$pHp$$ are the pH values for mother milk and plasma, and are $$7.2$$ and $$7.4$$ respectively.

In the project I'm using this formula for, I want to calculate the $$Mu/Pu$$ for various complex drugs. An example of this is the drug eplerenone, with the chemical formula $$\ce{C24H30O6}$$.

This drug has various pKa's, ranging from -4.2 to 16.44 (Source: DrugBank | Powering health insights with structured drug data. (March 6, 2023). DrugBank. https://drugbank.com/). I'm not very well versed (anymore) in this subject, and don't know which pKa to use. Most likely (to me) seems the pKa which is the closest to the pH of milk/plasma, but it could also be the pKa at which the relevant drug will be neutral.

Experimental data of emtricitabine, another drug with the formula $$\ce{C8H10FN3O3S}$$, shows for example an pKa of 2,65, according to the same source.

Can somebody help me with this question?

• Does this drug migrate between blood plasma and milk in neutral or ionic form ? There would be some distribution constant for this migration-active form and then 2 equlibriums between active and non-active form in each environment. Depending on that, higher pH in one environment can both favour or disfavour the drug presence there. // Perhaps take 2 pKa for anion-neutral and neutral-cation, and then take which is closer to biological pH. Mar 6 at 10:11