Abstract
We examined the changes in pharmacokinetics of an oral sustained-release theophylline preparation (Theolong®) during attacks of bronchial asthma. Ten patients (4 males and 6 females) were studied. They were admitted to the hospital because of attacks of bronchial asthma despite administration of an oral sustained-release theophylline preparation in the emergency outpatient clinic. After admission, serum concentrations of theophylline during the attack and during remission were measured in each patient, and the pharmacokinetic parameters at both stages were analyzed bythe Bayesian method. The serum concentrations of theophylline were 14.4±0.7μg/ml during the attack and 18.1±3.2μg/ml during remission; hence, the serum concentration of theophylline was decreased during the attack. The systemic clearance of theophylline was 0.044±0.0151/kg/hr during the attack, and 0.037±0.0181/kg/hr during remission; hence, clearance of theophylline was elevated during the attack. The volume of distribution (Vd) was 0.429±0.0241/kg during the attack and 0.399±0.0461/kg during remission; hence, an increased volume of distribution was noted during the attack. Furthermore, there was a correlation (r=-0.65) between the volume of distribution and the arterial pH level. Theophylline shows pH-dependent protein binding, so there is a possibility that the volume of distribution was increased by the protein binding rate which was affected by the changes in arterial pH level. No significant difference was noted in absorption lag time between the two stages. During the course from attack to remission, pharmacokinetics of theophylline undergo changes and affect serum concentrations, thus inducing easier development of adverse reactions. The above results suggest the importance of modifying doses when necessary after the attack stage while monitoring serum concentrations of theophylline.
