*4.1. Absorption*

PTS has high membrane permeability due to its specific features, including lipophilicity, low polar surface area, rotatable bonds, and hydrogen-bond acceptors and donors [3]. PTS has poor solubility in water (around 21 μg/mL), which can be overcome by solubilizing it with piperazine at a 2:1 stoichiometric molar ratio. Piperazine–PTS cocrystals had six

times greater solubility than PTS alone [26]. Moreover, administering PTS after a meal was observed to increase its oral absorption, as food consumption leads to the acceleration of bile secretion, which enhances the aqueous solubility of drugs co-administered with food [24]. The bioavailability of PTS has also been reported to be enhanced by using it in combination with a 2-hydroxypropyl-β-cyclodextrin (15 mg/kg) solution [25]. Notably, following oral administration, PTS exhibited higher bioavailability than resveratrol, with greater total plasma levels of its metabolites and parent compound [4].
