Hepatic elimination of femoxetine in pig

Hepatic elimination of femoxetine was studied in seven anaesthetized 40 kg pigs by means of constant rate infusions of 3-41 mg/min. (8.6-118 mumol/min.) into the portal vein. The elimination followed saturation kinetics (Michaëlis-Menten constants: Vmax 12 mg . min.-1 . kg-1 liver; Km 1.3 mg . 1-1 blood) and was characterised by high hepatic extraction, due to metabolism. The hepatic output of the active metabolite, nor-femoxetine, was very low, indicating that other metabolic pathways than demethylation were more important in the pig. The high hepatic elimination in the pig corresponds to the high first pass effect, earlier found in man, and it depends upon the infusion rate as well as the total dose.