Pharmacokinetics and effects of formoterol fumarate in healthy human subjects after oral dosing.
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.


CONCLUSIONS
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.
van den Berg
B T
BT
Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Braat
M C
MC
van Boxtel
C J
CJ
D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004804:Eosinophils / Q000378:metabolism*; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D011188:Potassium / Q000097:blood*; D012016:Reference Values; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D011188:Potassium; D000068759:Formoterol Fumarate