Pharmacokinetics of micronized and water dispersible palmitoylethanolamide in comparison with standard palmitoylethanolamide following single oral administration in male Sprague-Dawley rats.

Background: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide signaling molecule that may indirectly modulate the endocannabinoid system. It has poor water solubility and, therefore, is not readily absorbed in the human body. Various formulation techniques have been developed to enhance the rate of dissolution of PEA and minimize the variability of drug absorption when administered orally. The present study compared the pharmacokinetics (PKs) of two different grades of micronized PEA, a water-dispersible PEA, and standard PEA in male Sprague-Dawley rats, following a single oral administration.

Materials and methods: The drug PKs of each form of PEA-micronized (PEA-10µm), micronized PEA 6 µm (PEA-6 µm), and water-dispersible PEA (PEA-WD), were assessed and compared against a standard nonmicronized PEA (PEA-nm) using male Sprague-Dawley rats after a single dose oral administration. PEA plasma concentration (ng/mL) across all groups was determined using the liquid chromatography with tandem mass spectrometry method.

Results: PEA supplementation significantly increased the total area under curve (AUC) in all the groups compared to PEA-nm, with PEA-WD (P < 0.001) exhibiting an exceptionally large effect of > 16 times. In addition, the PEA supplementation raised the maximum concentration (Cmax) from the baseline in all the groups. When Cmax for each group was compared against PEA-nm at a probability level of 0.05, PEA-10 µm indicated no statistically significant difference (P = 0.060), whereas PEA-6 µm (P < 0.001) and PEA-WD (P < 0.001) displayed a statistically significant difference at the aforesaid probability level.

Conclusion: PEA-WD demonstrated a higher total AUC and Cmax, followed by PEA-6 µm and PEA-10 µm compared to nonmicronized form of PEA. This indicates greater bioavailability of water-dispersible PEA, thus making it a promising candidate for enhancing clinical outcomes.