van den Berg B T, Braat M C, van Boxtel C J
Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Eur J Clin Pharmacol. 1998 Aug;54(6):463-8. doi: 10.1007/s002280050494.
To evaluate the effects of formoterol after oral administration on plasma eosinophils and plasma potassium in healthy subjects.
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.
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.
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.
评估口服福莫特罗对健康受试者血浆嗜酸性粒细胞及血浆钾的影响。
对8名健康受试者口服168微克福莫特罗后7小时内，测定其血浆福莫特罗浓度、外周血嗜酸性粒细胞计数及血浆钾。4名受试者采用一级吸收的单室药代动力学模型，另外4名受试者采用双室模型，给出福莫特罗浓度-时间过程的描述。采用“效应室”方法的药代动力学/药效学（PK/PD）建模描述对钾和嗜酸性粒细胞的影响。
动力学参数值为：Ka：6.9（h⁻¹），t1/2：8.5（h），AUC：741（pg·h⁻¹·l⁻¹），V（area/f）：1470（l）。采用S型Emax模型将福莫特罗浓度与动态数据相关联。
口服福莫特罗后可在健康受试者血浆中检测到其浓度。这些数据可用于描述血浆钾和嗜酸性粒细胞的浓度-效应关系。两种效应的EC50值相当，但k（e0）和n值存在显著差异。
