Assessment of clinical application of test-dose concept for theophylline in patients with respiratory failure.

The possibility of clinical application of test-dose concept for theophylline was assessed in 11 patients with serious underlying disease who required theophylline. Based on the pharmacokinetic parameters calculated from the single intravenous aminophylline administration, they received a continuous infusion of aminophylline in order to maintain about 10 micrograms/ml plasma which is considered to be the lowest therapeutic level. Plasma levels during a constant rate infusion were assayed at 6:00, noon, 18:00 and midnight on the 3rd or 4th day after the infusion had started. There were no significant differences among plasma levels at each sampling time, but plasma levels varied ranging from 5.1 to 24.8 micrograms/ml (12.1 +/- 5.5 micrograms/ml: mean +/- S.D.), which values were in disagreement with the predicted value in some cases. The correlations of the theophylline clearance ratio to dose, pH, arterial partial pressures of oxygen (Pao2) and carbon dioxide (Paco2) ratios, which were calculated by dividing the value during continuous infusion by the value at the test dose, were investigated to evaluate which factor largely contributed to the failure of this dosing method. Although the clearance ratio did not correlate to pH and Pao2 ratios, significant negative relationships were observed between the clearance ratio and the dose (p less than 0.05) or Paco2 ratios (p less than 0.02). In other words, the alternation of dose or Paco2 resulted in the change of theophylline clearance. These findings suggest that the test-dose concept should not be used in the seriously ill patients whose theophylline clearance can change easily in relation to dose and/or Paco2 change.