Hepatic Elimination of Femoxetine in Pig

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Abstract
Hepatic elimination of femoxetine [an antidepressant] was studied in 7 anesthetized 40 kg pigs by means of constant rate infusions of 3-41 mg/min (8.6-118 .mu.mol/min) into the portal vein. The elimination followed saturation kinetics (Vmax [maximum rate of metabolism] 12 mg/min per kg liver; Km 1.3 mg/1 blood) and was characterized by high hepatic extraction, due to metabolism. The hepatic output of the active metabolite, norfemoxetine, 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 1st pass effect, earlier found in man, and depends upon the infusion rate as well as the total dose.