Bioequivalence and Bioavailability Forum

Dear all,
I have some double peak concentrations in almost all plasma concentration vs time curves of hydroxichloroquine sulfate (BCS class III drug) both for a test and a reference products (IR formulations). A large variability has been previously described for this drug in the literature, but nothing can be found about double peak concentrations.

I wonder if it could be due to an absorption window. The only think I was able to found is that the logP value is about 3.85, logD values change from 0.66 (pH=7.4) to -3.67 (pH=5.2) and the Pkas of the drug are 9.67 and 8.27.

Then, I wonder if as the pH increases along the GI tract, higher absorption takes place due to higher non-ionized fraction of the drug and lipophylicity, all this resulting in a second absorption peak, usually higher than the first one. I have often seen such kind of profiles with depot complex such as for exemple procaine-penicilline , but not in cases as the current so that I am not sure that my hypothesis can be correct. I would appreciate your opinion about this.

helen