Oosterhuis B, Braat M C, Roos C M, Wemer J, Van Boxtel C J
Clin Pharmacol Ther. 1986 Oct;40(4):469-75. doi: 10.1038/clpt.1986.208.
The study of terbutaline pharmacodynamics in patients with asthma is hampered by interfering stimuli when steady-state methods are employed. With pharmacokinetic-dynamic modeling, many of these interferences can be avoided. Using this technique, we studied the effect of terbutaline on lung function in 10 asthmatic patients with greater than 15% lung function reversibility. Terbutaline plasma concentrations, forced expiratory volume in 1 second (FEV1) airway resistance (Raw), and specific airway conductance (sGaw) were measured before and during 7 hours after subcutaneous dosing with 0.75 mg terbutaline. A hyperbolic concentration-effect relation was found. Fitting the time course of the effects required an effect compartment in the integrated model. Thus the delay between plasma concentration and effect time course was characterized by the rate constant ke0. Essentially the same ke0 was found for FEv1, Raw, and sGaw, indicating that the concerning receptors are "localized" in the same pharmacokinetic compartment. Of the lung function measures, sGaw was less sensitive to terbutaline than Raw and FEV1, whereas the latter tended to be the most sensitive one.
在采用稳态方法时，哮喘患者中特布他林药效学的研究受到干扰刺激的阻碍。通过药代动力学 - 动力学建模，可以避免许多此类干扰。利用这项技术，我们研究了特布他林对10名肺功能可逆性大于15%的哮喘患者肺功能的影响。在皮下注射0.75 mg特布他林之前和之后的7小时内，测量了特布他林血浆浓度、一秒用力呼气量（FEV1）、气道阻力（Raw）和比气道传导率（sGaw）。发现了双曲线浓度 - 效应关系。拟合效应的时间进程需要在综合模型中有一个效应室。因此，血浆浓度和效应时间进程之间的延迟由速率常数ke0表征。对于FEV1、Raw和sGaw，发现了基本相同的ke0，表明相关受体“定位”在同一药代动力学室中。在肺功能测量中，sGaw对特布他林的敏感性低于Raw和FEV1，而后者往往是最敏感的。
