A physiologically based pharmacokinetic model for theophylline disposition in the pregnant and nonpregnant rat

Abstract

There are numerous studies which examine the disposition of theophylline from a traditional point of view. Information about the behaviour of drugs, including theophylline, is, however, very scarce when investigating the kinetics by means of a physiological flow model. This study is concerned with the development of a predictive analytical model for the pharmacokinetics of theophylline in nonpregnant and pregnant rats. This model postulates that specific organ or tissue masses may be simulated by compartments whose elements have physiological properties, e.g., tissue volumes, blood flow, and metabolic activity. A model has been developed that has blood, brain, hepatic, muscular, pulmonary, renal, and fetal tissues. With few exceptions, the agreement was good between predicted and calculated tissue data in the pregnant and nonpregnant rats. Finally, model simulations were performed to investigate the impact of different pulmonary extraction ratios on the concentration-time profile of theophylline in a “hypothetical” human patient.