Fast hepatic biotransformation of p-synephrine and p-octopamine and implications for their oral intake

Citrus aurantium (bitter orange) extracts have been used in products for weight management and sports performance. These extracts contain large amounts of p-synephrine and much smaller amounts of p-octopamine. Both protoalkaloids exert lipolytic and glycogenolytic activities at similar concentrations. The biotransformation of p-synephrine and p-octopamine is not as well-known as those of other adrenergic amines. For this reason transformation of these amines was investigated in the isolated perfused liver. Special attention was devoted to the single pass extraction of each compound as well as to the kinetics of uptake. The assay of the amines in the outflowing perfusate was done by means of high performance liquid chromatography (HPLC). The single pass extraction of p-synephrine was higher than 90% at a portal concentration of 10 μM. It declined with the concentration, but was still around 30% at the concentration of 500 μM. At low concentrations (10-50 μM) the decreasing sequence of single pass extractions was p-synephrine > p-octopamine ≈ epinephrine > norepinephrine. Rates of uptake versus p-synephrine concentration resulted in a Michaelis-Menten type of relationship, with a KM value of 290.7 ± 32.1 μM and a Vmax of 0.762 ± 0.042 μmol min(-1) g(-1). The rates of uptake of p-octopamine did not present clear saturation and could be approximated by a linear relationship with a first order rate constant of 1.5 min(-1). The rapid hepatic transformation of p-synephrine and p-octopamine means that their concentration in the portal vein exceeds that in the systemic circulation during absorption. Their metabolic effects will, thus, be exerted predominantly in the liver.