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Pharmacokinetic‐pharmacodynamic modeling of terbutaline bronchodilation in asthma
Author(s) -
Oosterhuis Berend,
Braat M C Paul,
Roos Carel M,
Werner Johan,
Van Boxtel Chris J
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.208
Subject(s) - terbutaline , bronchodilation , pharmacokinetics , pharmacodynamics , airway resistance , anesthesia , bronchodilator , asthma , medicine , chemistry , pharmacology , airway
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 (FEV 1 ) airway resistance (Raw), and specific airway conductance (sGaw) were measured before and during 7 hours after subcutaneous dosing with 469.75 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 keO. Essentially the same keO was found for FEv l, 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 FEV l, whereas the latter tended to be the most sensitive one. Clinical Pharmacology and Therapeutics (1986) 40, 469–475; doi: 10.1038/clpt.1986.208