PharmaInformatics Unit, ATHENA Research Center, Athens, Greece.
Department of Pharmaceutical Sciences, State University of New York (SUNY), Buffalo, New York, USA.
Pharm Res. 2020 Sep 4;37(10):187. doi: 10.1007/s11095-020-02894-w.
PURPOSE: To demonstrate that oral drug absorption is terminated in finite time. To develop models based on biopharmaceutical/physiological and finite absorption time concepts.
The models are based on i) the passive drug diffusion mechanism under the sink conditions principle ii) the rate limiting role of the drug's properties solubility and permeability and iii) the relevant restrictions associated with the gastrointestinal transit times of drug in the stomach, the small intestines and the colon. Two input functions of constant rate are considered for the absorption of drug from i) the stomach/small intestines with an upper limit of 5 h and ii) the colon with an upper limit of 30 h. Branched differential equations were written for the time course of drug in the body.
Simulations were performed using different scenarios, assuming a variety of drug properties and limited or non-existent absorption from the colon. Literature oral data of cephradine, ibuprofen, flurbiprofen and itraconazole were analyzed. For all drugs examined, nice fittings of the branched differential equations to the experimental data were observed.
For all drugs the absorption process was terminated in the small intestine. The meaning of partial AUCs, Cmax, tmax are questioned. Applications of these models to IVIVC are anticipated.
目的：证明口服药物吸收在有限的时间内终止。基于生物制药/生理和有限吸收时间的概念开发模型。
这些模型基于以下原理：i）在吸收池条件下药物扩散的被动机制；ii）药物的性质溶解度和渗透性的限速作用；iii）与药物在胃、小肠和结肠中的胃肠道转运时间相关的限制。对于药物从 i）胃/小肠中的吸收，考虑了两种恒定速率的输入函数，上限为 5 小时；ii）对于结肠，上限为 30 小时。为药物在体内的时间过程写了分支微分方程。
使用不同的场景进行了模拟，假设药物的各种性质以及从结肠有限或不存在吸收。分析了头孢拉定、布洛芬、氟比洛芬和伊曲康唑的文献口服数据。对于所有检查的药物，分支微分方程对实验数据的拟合都很好。
对于所有药物，吸收过程都在小肠中终止。部分 AUC、Cmax、tmax 的意义受到质疑。预计这些模型将应用于 IVIVC。
