tailieunhanh - The population pharmacokinetics of D-β-hydroxybutyrate following administration of (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate

The administration of ketones to induce a mild ketosis is of interest for the alleviation of symptoms associated with various neurological disorders. This study aimed to understand the pharmacokinetics (PK) of D-β-hydroxybutyrate (BHB) and quantify the sources of variability following a dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester). Healthy volunteers (n = 37) were given a single drink of the ketone monoester, following which, 833 blood BHB concentrations were measured. Two formulations and five dose levels of ketone monoester were used. A nonlinear mixed effect modelling approach was used to develop a population PK model. A one compartment disposition model with negative feedback effect on endogenous BHB production provided the best description of the data. Absorption was best described by two consecutive first-order inputs and elimination by dual processes involving first-order (CL = L/h) and capacity limited elimination (Vmax = 4520 mg/h). Covariates identified were formulation (on relative oral bioavailable fraction and absorption rate constant) and dose (on relative oral bioavailable fraction). | The population pharmacokinetics of D-β-hydroxybutyrate following administration of R -3-Hydroxybutyl R -3-hydroxybutyrate