PHARMACOKINETICS AND EFFECTS OF FORMOTEROL FUMARATE IN HEALTHY-HUMAN SUBJECTS AFTER ORAL DOSING

Objective: To evaluate the effects of formoterol after oral administra tion on plasma eosinophils and plasma potassium in healthy subjects. M ethods: Plasma concentrations of formoterol, peripheral eosinophil cou nt and plasma potassium were determined during 7 h after oral administ ration of 168 mu g of formoterol to eight healthy subjects. Descriptio ns of the concentration-time course of formoterol are given using a on e-compartment pharmacokinetic model with first-order absorption in fou r subjects and a two-compartment model in the other four subjects. Eff ects on potassium and eosinophils are described using pharmacokinetic/ pharmacodynamic (PK/PD) modelling with the 'effect-compartment' approa ch. Results: The values of the kinetic parameters were: Ka: 6.9 (h(-1) ), t(1/2) 8.5 (h), AUG: 741 (pg . h(-1) . l(-1)), V-area/f: 1470 (1). Formoterol concentrations were related to dynamic data using a sigmoid E-max model. Conclusion: Plasma concentrations of formoterol call be measured in plasma of healthy subjects after oral administration. Thes e data can be used for describing concentration-effect relations with respect to plasma potassium and eosinophils. With comparable EC50 valu es for the two effects, remarkable differences were found for k(e0) an d n values.