Aesculin Oral Absorption Characteristics And Pharmacokinetics Studies

Purpose:To provide basis for industrialization and clinical application of aesculin in primary hyperuricaemia,investigated the equilibrium solubilities,apparent oil/water partiton coefficients,absorption mechanism in rats'intestine and pharmacokinetical contrast of aesculin between two administration routs(ip injection and ig injection)and specified dose (100mg·kg-1)Methods:A high performance liquid chromatography was established to detect the concentration of aesculin in all solutions.The apparent partition coefficient of aesculin for n-octanol/water or buffer solution systems were determined by shaking flask method. SPIP method was used to investigated the influence of low/medium/high concentrations and different segments on intestinal absorption of aesculin in rats.A high performance liquid chromatography established to determine the concentration of aesculin in rats'plasma was applied for pharmacokinetics in two administration routs and specified dose.Results:When pH belows 6, the equilibrium solubilities,apparent oil/water partiton coefficients of aesculin was not sensitive to pH in water phase and changed little as x±SD showed 2.95±0.44,0.65±0.02.When pH above 6.8, the equilibrium solubilities,apparent oil/water partiton coefficients of aesculin increased and decreased as pH raised up respectively,the x±SD showed 6.95±3.52,-1.14±0.32. There was no statistical discrepancy of Ka and Papp between different concentrations in duodenum and jejunum,yet ileum existed. The Ka and Papp in concentration of 80 mg·L-1 was arranged as follows:duodenum≈jejunum > ileum, duodenum> jejunum> ileum.The pharmacokinetics fited first-order and mono-compartment model,the critical parameters shown as below:ip injection ka=8.7155±1.0360/hour, k=1.3774±0.1298/hour, Cmax=164.3693±16.93 mg·L-1, Tmax=0.167hour, T1/2(k)=0.5068±0.0475hour, AUC0â†'∞=149.6423±20.7139mg·h·L-1, CL=0.1396±0.0295 L·h-1; ig injection: ka=8.2169±1.8475/hour, k=0.8282±0.2155/hour, Cmax=2.6286±0.6012 mg·L-1, Tmax=0.167hour, T1/2(k)=0.8801±0.2094hour, AUC0â†'∞=3.7636±0.4384mg·h·L-1, CL=5.7681±0.4598 L·h-1.Conclusion:Dissolution of aesculin should not be the speed-limit process to its absorption. Aesculin, a better hydrophilic compound compared to its bad liposolubility, leads to an absorption problem when penetrating the lipid bilayers in intestines. The absorption mechanism in rats'upper-intestine(duodenum and jejunum)is simple diffusion,while unclear that need to further investigate in rats' ileum. The difference of pharmacodynamics action caused by variant administration routs depends on its absorption and tissue distribution.