Pharmacokinetics of absorption, distribution and elimination of fenfluramine and its main metabolite in man

Abstract

Previously reported data (Beckett & Brookes, 1967) for the excretion of (±)-fenfluramine and its main metabolite, norfenfluramine, have been examined pharmacokinetically using an analogue computer. A three compartment open model was proposed to simulate the biological processes with one peripheral compartment rapidly equilibrating with the central compartment and the second (tissue) compartment only slowly attaining equilibrium. Good agreement between experimental and computed data was obtained, although marked inter-subject variation was recorded. This was attributed to inter-subject differences in the three body compartments. Differences between the pharmacokinetic parameters obtained after oral and intravenous administration of fenfluramine indicated that the drug was significantly N-dealkylated in the intestine or on a first-pass through the liver.