A comparison of absorption rate models in the prediction of steady-state plasma concentrations during oral theophylline administration

During therapy with oral controlled released theophylline/aminophylline, steady-state plasma drug concentrations may be predicted by fitting estimates of patient pharmacokinetic parameters to a pharmacokinetic model. The choice of model requires an assumption about the type of rate reaction of the drug absorption process (zero order to first order). In 10 subjects, plasma theophylline concentrations after a single intravenous dose of aminophylline were used to make individual estimates of drug clearance and volume of distribution. Each subject then received oral controlled release theophylline ('Theo-Dur', Fisons Pharmaceuticals plc) and steady-state pre-dose and post-dose plasma concentrations were determined. Predictions of steady-state plasma theophylline concentrations using pharmacokinetic models based on first-order (Model A) and zero order (Model 01) drug absorption were compared. Model A and Model 01 each underestimated the pre- and post-dose steady-state plasma drug concentrations. However, Model 01 was more accurate in predicting post-dose drug concentrations, whilst Model A demonstrated better precision in the prediction of pre-dose drug concentrations at steady-state (P < 0.05).