Pharmacokinetic-pharmacodynamic modeling of terbutaline bronchodilation in asthma

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Abstract
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 > 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 FEV11, whereas the latter tended to be the most sensitive one.