Borisyuk I. Pharmacokinetic and biopharmaceutical analysis of bioavailability of drugs with different mechanisms of absorption (the experimental and computer modeling studies).

Dissertation is devoted to developing methodologies of pharmacokinetic and biopharmaceutical studies to create innovative medicines and improving their generic forms and methods of state registration. During the work it was shown that the appearance of double peaks in drug concentration in plasma of experimental animals and humans is due to their transit along the gastrointestinal tract (the existence of two windows of absorption, reabsorption, gastro–hepatic circulation, metabolism). Based on experimental studies, the concept of reversible metabolic, transport and related physiological model bioavailability of drugs. For example, some drugs proved using dissolution test (in vitro), as a means of experimental evaluation of bioavailability generic drugs. Biopharmaceutical approach was used to develop sublingual drug form Hidazepam IC and Paracod IС. The study presents a new reliable tool for determining the bioavailability of drugs or their generic counterparts, which combines the reliability of many famous QSPR models and eliminates their disadvantages. Based on obtained model the role of various fragments of 1,4–benzodiazepine structure that affect the parameters of the half–life of drugs was defined. Structural factors of drugs were identified, knowledge of which makes it easier to refer them to the appropriate class of BCS. It is shown that using the method of classification trees is quite promising tool for preliminary analysis of the potential bioavailability of drugs whose absorption occurs by simple diffusion.