System for clinical pharmacokinetic monitoring of theophylline therapy

A system was developed for guiding theophylline therapy in acutely ill patients with respiratory disease and for recovery of pharmacokinetic information. A dosage regimen nomogram was designed based on literature data and preliminary pharmacokinetic studies in patients. Using the nomogram, physicians select the loading and infusion dosages based on previous therapy, body weight, age, and cardiac and hepatic status of the patient. Specifications are provided for loading (up to 5.6 mg/kg) and maintenance doses (0.9, 0.68, or 0.45 mg/kg/hr) of aminophylline, handling of i.v. dosage forms, and collection of three initial blood samples. Serum samples were assayed for theophylline by high-performance liquid chromatography for rapid feedback of data to the physician and computer estimation of body clearance values. The usefulness of the nomogram guidelines was examined prospectively in 72 patients. Near-steady-state serum concentrations in the therapeutic range of 8-20 mg/liter were found in 72% of the patients. Only two patients were outside of the range of 5-25 mg/liter. The relationship between the physician's estimate of the patient's clinical status (three classes) and measured body clearance was highly significant (p less than 0.025). A comprehensive data collection format allows further analysis of the factors responsible for the variability in theophylline disposition in patients undergoing therapy.