Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects

This study gave healthy human volunteers the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in a meal replacement drink as a single dose of 140, 357, or 714 mg/kg, and at those doses three times daily for 5 days. Plasma beta-hydroxybutyrate and acetoacetate rose, and the intact ester was not detected. At the highest dose, peak levels were reached within 1 to 2 hours at 3.30 mM for beta-hydroxybutyrate and 1.19 mM for acetoacetate. Elimination half-life ranged from 0.8 to 3.1 hours for beta-hydroxybutyrate and 8 to 14 hours for acetoacetate. The ester was generally well tolerated, with some gastrointestinal effects when large volumes of milk-based drink were consumed at the highest dose.