A phiarmacokinetic model, involving first-order processes for drug release, absorption, and elimination, may be used for the description of the behavior of sustained-release preparations consisting of slowly and immediately available fractions. The shift of the rate-determining step, as the relative rates of absorption and release are changed, can be shown both mathematically and by analog computer simulation. These theoretical results are used for interpretation of experimental data with a new sulfa drug of low solubility, 2-sulfanilamido-5-methyl-pyrimidine, compressed tablets of which behave as a sustained-release preparation.
HE WTDESPREBD use of sustained-release and Tdepot pre~mrations in drug therapy has made the full understanding of their actions and properties of considerable importance. A number of publications concerned with the actions, the properties, and the importance of such a full understanding h a w appeare.d in the last decade [viz., Dost (X), Lazarus and Cooper (3), Levy et ul. (+ti), Nelson et al. (7-9), Parrott (lo), Robinson and Swintosky (ll), Sjogren and Ostholm (12), Wagner et al. (13), Wiegand and Taylor (14), and others].
The most useful method for the examination of the interrelationships between drug preparations and the human body has been found to be through the use of a mathematical model, first fitting it to the actual data, and then examining the model found most useful for its functional behavior. :In this way the important implications of the model may be discovered and those found important checked by further laboratory experiments. Because of the complexity of +he differential equations involved, direct mathematical study is not always the most useful manner of determining the implications of a mathematical model for absorption, distribution, and excretion, and it has often been found more conveni'ent to make use of an electronic analog computor [see Fish ( l G ) , Pace (17), and Garrett el al. (IS)].
A recent paper by Taylor and Wiegand (15) was concerned with the analog investigation of the following model, which has been found to describe suitably the behavior of sustainedrelease preparations from which a certain fraction, f r , of the administered dose becomes available ____