Evaluation of theophylline therapeutic drug monitoring service

Abstract

Background: Terapeutic monitoring of the-ophylline serum levels is required due to its narrow therapeutic range and marked interindi-vidual pharmacokinetic variability. We evaluated therapeutic drug monitoring service for theoph-ylline in Slovenian clinical setting, which currently includes no pharmacokinetic evaluation of measured theophylline serum concentrations. Methods: We retrospectively evaluated 127 randomly selected theophylline serum level determinations performed in 2010 in a tertiary clinical setting in Slovenia. Demographic data, information on theophylline dosing and blood sampling were collected from patients’ data fles. Authors evaluated the appropriateness of the following procedures: indications for theophylline serum concentration measurement, timing of blood sampling and dosage adjustments made after theophylline levels had been reported. On the basis of collected data, a population pharma-cokinetic model for theophylline was built and further used for the evaluation of dosage adjustments. Results: Out of 127 cases, 107 (84.3%) had clinically justifed indication for theophylline serum level measurement. Near half of the measurements (44.9%) were performed before the steady state of theophylline concentrations was established. 65% of measured concentrations were subtherapeutic and the average measured concentration was below the therapeutic range (53.1 μmol/L). Despite subtherapeutic concentrations, the dose of theophylline was generally not increased. Pharmacokinetic model enabled the calculation of average optimal daily dose which was signifcantly higher than the  average actual daily dose used (876 mg vs. 572 mg, p < 0.001). Conclusions: Teophylline TDM service should be optimized and pharmacokinetic interpretation of theophylline serum levels should be integrated into clinical practice.