雌二醇甲基化-β-环糊精包合物鼻黏膜吸收动力学研究

目的研究雌二醇甲基化 β环糊精包合物鼻黏膜吸收动力学,考察循环液的体积和流速对雌二醇甲基化 β环糊精包合物鼻黏膜吸收的影响。方法采用大鼠在体灌流模型,并固定循环液体积和流速。结果吸收速度常数(k)随着循环液体积的增加呈下降趋势;当流速较小时,随着流速的增加,k增大,但超过2 5mL·min-1后,k反而随着流速的增加而减小;循环液为5mL、流速2 5mL·min-1时,不同浓度的雌二醇甲基化 β环糊精包合物鼻黏膜吸收速度常数不同,且随药液浓度的增加而增大,经t检验(P <0 0 5 ) ,不同浓度间存在显著差异。结论雌二醇环糊精包合物鼻黏膜吸收具有浓度依赖性,在固定浓度条件下其动力学过程符合零级动力学模型,吸收速度常数与包合物的药物动力学解离 缔合平衡有关

Studies of estradiol-methyl-β-cyclodextrin complexes nasal absorption kinetics

Objective To investigate the regulation of estradiol-methyl-β-cyclodextrin complexes nasal absorption kinetics.Methods The nasal recirculation methods in situ was used as experiment model to study the regulation of estradiol-methyl-β-cyclodextrin complexes nasal absorption kinetics in rats.The perfusion volume and flow rate were fixed.Results The larger the perfusion volume,the smaller the percent absorbed at each time intervals.At first,the absorption rate constant K increased with the increase of flow rate,but when the flow rate was over 2.5 mL·min~ -1 ,k decreased significantly.Taking 5 mL as perfusion volume and 2.5 mL·min~ -1 as flow rate, Seven concentration levels 5,10,20,25,35,45, 60 mg·L~ -1 ,were selected for the study of nasal absorption. The results indicated that the absorption rate of different concentration are different significantly,k increased with the increase of the concentration.Conclusion The mechanism of estradiol nasal absorption is passive diffusion,follows zero-order kinetics.