Pharmacokinetics of Femoxetine in Man

Abstract

The pharmacokinetics of a structurally new 5HT[serotonin]-uptake inhibitor, femoxetine (FG 4963), with antidepressant properties were investigated in man using a radioactive as well as a non-labeled substance. A 2 compartment open model gives a good description of the data, both after oral and i.v. administration. The substance was almost completely absorbed after an oral dose, but only 5-10% reached the systemic circulation due to extensive first pass metabolism. The metabolites had distribution and excretion rates similar to the parent compound. Only a small part (< 2%) was excreted as femoxetine in the urine. The urinary excretion of the parent compound varied more than 100-fold depending on the pH of the urine. The urine pH did not influence the plasma concentration of femoxetine. Most of the substance (up to 80%) was eliminated by urinary excretion of metabolities, and only a small part of the radioactive dose was excreted in the feces (up to 11%). The pharmacokinetic parameters were not dose-dependent in the range investigated, but it was not possible to decide whether the bioavailability was dependent on the dose. The variation between subjects was rather large, giving only a limited possibility for prediction of the plasma concentration from one subject to another.