B T van den Berg1, M C Braat, C J van Boxtel. 1. Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Abstract
OBJECTIVE: To evaluate the effects of formoterol after oral administration on plasma eosinophils and plasma potassium in healthy subjects. METHODS: Plasma concentrations of formoterol, peripheral eosinophil count and plasma potassium were determined during 7 h after oral administration of 168 microg of formoterol to eight healthy subjects. Descriptions of the concentration-time course of formoterol are given using a one-compartment pharmacokinetic model with first-order absorption in four subjects and a two-compartment model in the other four subjects. Effects on potassium and eosinophils are described using pharmacokinetic/pharmacodynamic (PK/PD) modelling with the 'effect-compartment' approach. RESULTS: The values of the kinetic parameters were: Ka: 6.9 (h(-1)), t1/2, 8.5 (h), AUC: 741 (pg x h(-1) x l(-1), V(area/f): 1470 (l). Formoterol concentrations were related to dynamic data using a sigmoid Emax model. CONCLUSION: Plasma concentrations of formoterol can be measured in plasma of healthy subjects after oral administration. These data can be used for describing concentration-effect relations with respect to plasma potassium and eosinophils. With comparable EC50 values for the two effects, remarkable differences were found for k(e0) and n values.
OBJECTIVE: To evaluate the effects of formoterol after oral administration on plasma eosinophils and plasma potassium in healthy subjects. METHODS: Plasma concentrations of formoterol, peripheral eosinophil count and plasma potassium were determined during 7 h after oral administration of 168 microg of formoterol to eight healthy subjects. Descriptions of the concentration-time course of formoterol are given using a one-compartment pharmacokinetic model with first-order absorption in four subjects and a two-compartment model in the other four subjects. Effects on potassium and eosinophils are described using pharmacokinetic/pharmacodynamic (PK/PD) modelling with the 'effect-compartment' approach. RESULTS: The values of the kinetic parameters were: Ka: 6.9 (h(-1)), t1/2, 8.5 (h), AUC: 741 (pg x h(-1) x l(-1), V(area/f): 1470 (l). Formoterol concentrations were related to dynamic data using a sigmoid Emax model. CONCLUSION: Plasma concentrations of formoterol can be measured in plasma of healthy subjects after oral administration. These data can be used for describing concentration-effect relations with respect to plasma potassium and eosinophils. With comparable EC50 values for the two effects, remarkable differences were found for k(e0) and n values.