Evaluation of two methods for estimating theophylline clearance prior to achieving steady state

The Koup et al. and Chiou et al. clearance estimation methods were evaluated n 19 chronic obstructive pulmonary disease (COPD)/asthmatic patients who were receiving aminophylline by continuous infusion. Estimated theophylline clearance (Clest) was determined using two serum concentrations obtained during the first few hours of therapy (1-16 hr) prior to achievement of steady state. Actual theophylline clearance (Clact) was determined after steady state conditions had been 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 less than 0.001, and r = 0.858, p less than 0.001, respectively. The clearance estimation methods were compared with the Food and Drug Administration (FDA) dosage guidelines and shown to be clearly superior in predicting therapeutic steady state theophylline concentrations.