Pharmacokinetics of femoxetine in man

The pharmacokinetics of a structurally new 5HT-uptake inhibitor, femoxetine (FG 4963), with antidepressant properties have been investigated in man using a radioactive as well as a non-labelled substance. A two compartment open model gives a good description of the data, both after oral and intravenous 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 (less than 2%) was excreted as femoxetine in the urine. The urinary excretion of the parent compound varied more than a 100-fold depending on the pH of the urine. The urine pH, however, did not influence the plasma concentration of femoxetine. Most of the substance (up to 80%) was eliminated by urinary excretion of metabolites, and only a small part of the radioactive dose was excreted in the faeces (up to 11%). The pharmacokinetic parameters were not found to be 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.