ABSTRACT
The oral route is considered to be a complex and difficult route for administration and far from all drugs will enter the systemic circulation via the gastrointestinal (GI) membranes. This preclusion is due to the fact, in physiological aspects, that the GI tract has a function of absorbing food nutrients, electrolytes and water, yet at the same time is a very effective barrier against toxins, bacteria and foreign material (Kararli, 1989). In general, a large number of drugs entering the development phase or rather, during the phase-II-phase-III clinical trials, fail owing to lack of sufficient ADME (absorption, distribution, metabolism, excretion) and biopharmaceutical properties. The high attrition rate has highlighted the importance of screening for good pharmacokinetic properties as early as possible in the discovery process, e.g. during the lead identification phase. Known failures are mainly due to low solubility, poor permeability and extensive first-pass metabolism, both in the GI membranes and in the liver. Low oral availability of a drug can be associated with significant variability both between different treatment occasions and between different patients. Knowledge of the reasons for low bioavailability is, therefore, of great importance both for efficacy and safety in the treatment and for the development of follow-up candidates.
