Studies Of The Membrane Absorption And Preliminary Pharmacokinetic Of Liquiritin And Its Aglycon

new pharmacological activity and good potency in cardiovascular system. The purpose of this study was to explore the properties of absorption ,distribution , metabolism, the blood-brain barrier permeability and bioavailability of liquiritin and liquirtigenin , so as to make some contribution for new drugs development.Methods: (1) Marvin software of Chemaxon's Corporation was employed to forecast the chemical parameters of liquiritin and liquirtigenin, for example: pKa, LogP, LogD, PSA.(2) Intestinal transport of compounds were measured using the single pass intestinal perfusion technique in rats and Caco-2(MDCK)cell monolayers to examine the above compounds apparent penetration coefficient (Papp)and effective permeability values (Peff). (3)An in vitro model of BBB using cultured rat brain microvascular endothelial cells and astrocytes was established to study the permeability of the above compounds. (4) The metabolism of the above compounds were studied in vitro by incubation with human liver microsomes S9. (5) the bioavailability of liquirtigenin was determined using SD rat.Results: (1). Only MW and LogP of liquiritin were in the range of"rule of 5". The computational method was able to predict LogP and LogD of liquiritin within 0.6 log units for the experimental data. All physics and chemistry parameters of liquirtigenin were in the range of"rule of 5".(2)Liquiritin exhibited poor in situ and in vitro rat intestinal permeability and liquirtigenin appeared to be a higher permeability compared to liquiritin. Passive transcellular diffusion dominated the intestinal transport mechanism of liquiritin and liquirtigenin, with no evidence of P-glycoprotein involvement. (3) The quantity of in vitro BBB penetration of liquiritin, liquiritigenin, benzylpenicilin and chloramphenicol were 8.4±1.61%, 29.7±6.8%, 1.6±0.2% and 34.0±4.9%,within 90 minutes respectively. (4) Liquirtigenin was highly stable in incubation with human liver microsome. the CYP450 isozymes 2C9, 3A4 significantly were inhibited within 0～200μM. (5) Bioavailability of liquirtingenin was 31.19±7.15% in SD rat. Liquirtigenin was in the body fluids and tissues and organs widespreadly.Conclusion: The above results indicated that intestinal absorption,S9 metablism stability, BBB permeability and bioavailability of liquirtigenin are high.but liquiritin was not. These profiles of the two compounds may be the outcome of its undesirable physical and chemical properties. The primary methods of BBB permeability in early phase of drug discovery were established.