Determination of plasma and tissue distribution of 27-hydroxycholesterol after a single oral administration in a mouse model

The side chain 27-hydroxycholesterol (27OHC) has been reported to inhibit the replication of several pathogen viruses, including Herpes Simplex virus, Rhinovirus, Rotavirus and SARS-CoV-2, in in vitro and ex vivo models. Objective: in view of a future potential therapeutic use of 27-hydroxycholesterol 27OHC, a pilot pharmacokinetic study was set up. Methods: this active substance was complexed with 2-hydroxypropyl-β-cyclodextrin and orally administered in a single dose to CD1 male mice, then evaluating its recovery in plasma and a few tissues up to 24 h post-treatment. Results: the absorption of the oxysterol by the small intestine was moderate, due to its physicochemical properties, but still relevant and rapid, showing a peak 1 hour after supplementation and being almost completed 24 hours after treament. 27-Hydroxycholesterol 27OHC appeared to be a high hepatic extraction drug, possibly with an extrahepatic component contributing to the total clearance. Conclusions: following the oral 25 mg/kg dosing, plasma levels of 27-hydroxycholesterol 27OHC showed an average steady-state concentration similar to that inhibiting in vitro the replication of all the viruses tested so far. Significance: here reported are the first pharmacokinetic data relative to a natural oxysterol administered per os. Data that should contribute to further elucidate oxysterols pathophysiology and guide non-clinical studies aiming at investigating possible therapeutic use of 27OHC or its analogs.