Evaluation of Two Methods for Estimating Theophylline Clearance Prior to Achieving Steady State

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Abstract
The Koup, et al and Chiou, et al clearance estimation methods were evaluated in 19 chronic obstructive pulmonary disease (COPD)/asthmatic patients who were receiving aminophylline by continuous infusion. Estimated theophylline clearance (Clest) was determined using 2 serum concentrations obtained during the 1st few hours of therapy (1-16 h) prior to achievement of steady state. Actual theophylline clearance (Clact) was determined after steady state conditions were achieved (defined as 4-5 half-lives at the same infusion rate). The correlation between Clact and Clest was highly significant for both the Koup, et al and Chiou, et al methods, r = 0.865, P < 0.001 and r = 0.858, P < 0.001, respectively. The clearance estimation methods were compared with the USA Food and Drug Administration dosage guidelines and shown to be clearly superior in predicting therapeutic steady state theophylline concentrations.