In vivo pharmacokinetic evaluation of Veech ketone monoester and metabolites in rats after IV (bolus and infusion) and oral administration.

Multiple exogenous supplements to achieve ketosis using the oral route have been developed to elevate blood BHB levels on demand and in a controllable fashion. The focus is now shifting to evaluating these supplements as potential therapeutic agents and developing strategies to not only achieve ketosis but also maintain it. One such strategy is to administer these as a continuous IV infusion. The main ingredient of one popular exogenous ketone supplement, Veech ketone monoester (KE), was administered via the IV (bolus and infusion) and oral routes to SD rats. The plasma concentration vs. time profile of not only KE but also its immediate metabolites- BHB, 1,3-BD, and AcAc were tracked and used to estimate pharmacokinetic parameters of these molecules. The data from oral and IV bolus administration were used to calculate the oral bioavailability of all molecules. It was seen that KE showed very rapid clearance with a half-life of about 2-3 mins. BHB had a half-life of about 13 mins, while AcAc and 1,3-BD showed a longer half-life of about 23 and 26 mins, respectively. The oral absolute bioavailability of KE itself was extremely low at about 3%. The volume of distribution for all molecules was slightly more than the volume of the central blood compartment in male rats. The administration of KE via the oral and IV routes lowered the blood glucose level in a manner inversely mirroring the elevation of plasma BHB levels. Plasma chemistry of the rats after a 24-hour continuous infusion of KE was assessed. There was no significant change in the plasma pH, but there was a significant reduction in blood glucose levels and blood urea nitrogen levels.