Chromatographic methods in predicting oral drug absorption

Abstract

Today with the development of combinatorial chemistry hundreds and hundreds of compounds that have potential biological activity are synthesized. The studies which include the selection of drug candidates and the study of their pharmacological properties are time consuming, expensive and usually require the use of experimental animals. For ethical and/or economical reasons, a great deal effort is currently being made to develop in vitro systems and provide primary information about the capability of new compounds in the first steps of drug development. Chromatographic models to predict drug absorption are experimentally easier than membrane-based permeability assays, because of their simplicity, accuracy and avoidance of experimental animals. Different chromatographic systems have been proposed to predict oral drug absorption. The use of conventional reversed-phase columns only has proven to provide adequate correlations for homologous series of compounds. The inclusion of amphiphilic structures in the stationary and/or mobile phases is a pre-requisite to emulate interactions of drugs with the phospholipids bilayers in the membranes.

Savremeni razvoj kombinatorijalne hemije omogućio je sintezu velikog broja jedinjenja sa potencijalnom biološkom aktivnošću. Ispitivanja koja uključuju izbor jedinjenja i studije farmakoloških osobina su dugotrajna, skupa i obično zahtevaju primenu eksperimentalnih životinja. Iz etičkih i/ili ekonomskih razloga, veliki napori ulažu se u razvoj in vitro sistema koji mogu da pruže značajne informacije u ranim fazama razvoja leka. Hromatografski modeli za predviđanje apsorpcije leka su eksperimentalno jednostavni, tačni i ne zahtevaju primenu eksperimentalnih životinja. Primena reverznofaznih hromatografskih sistema dala je dobre korelacije samo za homologe serije jedinjenja. Uvođenje amfifilnih struktura u stacionarnu i/ili mobilnu fazu je bitan uslov za simulaciju interakcija farmakološki aktivnih jedinjenja sa fosfolipidnim dvoslojem u membrani.