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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Abstract
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 (Cmax) data based on the two absorption models. There was a highly significant relationship between observed and calculated time to Cmax 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.

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