Variation in theophylline clearance rate with time in chronic childhood asthma.

Wide theophylline clearance rate (TCR) range between different individuals has been reported, but little is known about its change with the passage of time. Optimal theophylline therapy for asthma aimed at plasma or serum levels of 10 to 20 microng/ml is now strongly recommended. Significant TCR variability with time might easily result in theophylline levels in the toxic or subtherapeutic ranges. Thirty severe asthmatics (mean age, 13 yr) received 24 hr constant intravenous infusion of 1 mg/kg/hr aminophylline USP. TCR was determined after a steady state was reached. Twelve of these patients with persisting poorly controlled asthma underwent repeat infusion for TCR determination at intervals of 1 to 8 mo (mean, 4.7 mo). When these results were compared to the initial individual TCR, the mean absolute change was 28 +/- 24% (mean +/-SD). Thus, this significant individual variation in TCR with the passage of time (p less than 0.01) requires periodic monitoring of plasma theophylline levels in severe asthma treated by optimized theophylline dosage.