Studies on the Absorption Kinetics of Theophylline in the Steady State, Following Multiple Oral Dosing of a Sustained-Release Theophylline Tablet Formulation to Asthmatic Patients

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The pharmacokinetics of theophylline in the steady state, following multiple oral dosing of a sustained-release theophylline tablet formulation, were studied in six asthmatic patients. The pharmacokinetic parameters were calculated by utilizing a one-compartment model with zero-order of first-order absorption according to the Davidon-Fletcher-Powell method. The computer-predicted theophylline concentrations based on the zero-order absorption model fitted the observed data points better than those based on the first-order absorption model. The nonlinear least-squares curve based on the first-order absorption model underestimated the maximum observed plasma concentrations of theophylline. Linear relationships were obtained between observed and calculated maximum plasma concentration (C_<max>) data based on the two absorption models. There was a highly significant relationship between observed and calculated time to C_<max> data based on the zero-order absorption model. These results show that the drug absorption from the sustained-release theophylline tablet formulation used in this study is best described by an apparent zero-order rather than a first-order absorption model.
1986-09-25