Appropriateness of Theophylline Plasma Levels

To the Editor.—Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 60 years and remains one of the most widely prescribed drugs for the treatment of airway diseases worldwide. As with other drugs,1 theophylline monitoring is crucial because of its narrow therapeutic index, but it should only be performed once the pharmacologic steady state has been achieved.2 Although the therapeutic range varies widely because of the interindividual variability in pharmacokinetics, a concentration between 10 and 20 μg/ mL has the greatest likelihood to achieve maximal benefits safely. Plasma concentrations greater than 20 μg/mL are associated with toxic symptoms.3 Occasional evidence has been provided that inappropriate prescribing might occur with frequency and might persist over time.45 Because we aimed to assess the appropriateness of plasma theophylline levels for developing educational policies at our institution, we reviewed theophylline determinations for inpatients and outpatients performed between January and December 2006 at the Verona University Hospital, which has 750 beds and serves an area with a population of 270 000 inhabitants. The main outcome was established as the proportion of theophylline levels outside the therapeutic range. A total of 240 theophylline plasma levels were assayed for inpatients (199; 83%) and outpatients (41; 17%) during the 12-month study period. Inappropriate levels could be detected in 154 (64.2%) samples, 29 (12.1%) corresponding to toxic concentrations and 125 (52.1%) to subtherapeutic values. Overall, the percentage of measurements within the therapeutic range was statistically higher for inpatients than for outpatients (37.2% vs 29.3%, P < .001 by chi-square test) (Table). Results of this investigation attest that nearly two thirds of theophylline measurements performed in our clinical laboratory are outside the therapeutic range, which might reflect either tests requested in patients not receiving the drug or inadequate timing of sampling.3 Because inappropriate indications or wrong sampling time may produce misleading results, educational strategies to enable the appropriate use of therapeutic monitoring of theophylline are needed to prevent adverse clinical outcomes and save economical resources.