DISPOSITION OF THEOPHYLLINE AFTER A SINGLE INTRAVENOUS-INFUSION OF AMINOPHYLLINE

Abstract

Theophylline serum concentration and disposition after a single 30 min i.v. infusion of 7.4 .+-. 1 mg anhydrous theophylline/kg of body wt were determined in 20 otherwise healthy adult asthmatic volunteers using high-pressure cation-exchange chromatography. This dose resulted in a mean peak serum concentration of 18 .+-. 3.3 .mu.g/ml, which remained < 10 .mu.g/ml for 6 h and > 5 .mu.g/ml for the entire 12 h period of observation. The rate of theophylline elimination in these subjects was generally slower than previously reported. Among the 4 cigarette smokers, but theophylline plasma clearance was significantly (P < 0.001) more rapid than that observed in the 16 nonsmokers. Theophylline clearance was highly correlated with elimination half-life (r = 0.83, P < 0.001). These data support previous recommendations for an i.v. loading dose of 5 mg theophylline/kg of body wt (6 mg aminophylline/kg) when a mean increase in serum concentration of approximately 10 .mu.g/ml is desired. Based on the clearances obtained, a constant infusion rate of 0.4 mg/kg per h (0.5 mg of aminophylline/kg per h) is likely to maintain a mean serum concentration of 10 .mu.g/ml among nonsmoking adults without cardiovascular or liver disease. Previous recommendations for a continuous infusion of 0.9 mg of aminophylline/kg per h appear to be excessive, except for otherwise healthy children and cigarette-smoking adults. Even using this lower recommendation for continuous infusion, but therapy beyond 12-24 h may still result in sufficient accumulation of drug to place some patients at risk for toxicity. If theophylline is required beyond the initial treatment of acute symptoms, continued therapy should be guided by serum theophylline measurement.