Are theophylline "levels" a reliable indicator of compliance?

Clinicians frequently rely on serum theophylline concentrations (STCs) as an indicator of compliance for asthma medications. Most patients with good compliance do not have excessive fluctuations during routine STC monitoring. However, our experience is that in certain patients, persistently low or erratic STCs may be a sign of abnormal theophylline disposition. With careful analysis of theophylline absorption (STC every 2 hours for 24 hours after oral theophylline doses) and elimination (serial STC for 12 hours after an intravenous dose of aminophylline), we identified several patients with previously unrecognized anomalies of theophylline pharmacokinetics. These include (1) a 16-year-old girl with consistent temporal fluctuation in STCs during administration of a sustained-release formulation every 8 hours because of delayed absorption and enhanced elimination of theophylline at night, (2) a 13-year-old girl with markedly delayed absorption of a once-daily preparation administered in the evening, (3) a 5-year-old boy with erratic absorption of a liquid theophylline preparation with significantly increased STCs during the night, and (4) a 49-year-old man with 60% bioavailability of aminophylline tablets. Based on these observations, we suggest that clinicians carefully consider the possibility of abnormalities in theophylline disposition before assuming unexpected deviations in STCs are solely the result of noncompliance.