Yu L X, Amidon G L
College of Pharmacy, The University of Michigan, Ann Arbor, USA.
Eur J Pharm Biopharm. 1998 Mar;45(2):199-203. doi: 10.1016/s0939-6411(97)00088-x.
This report describes an extended compartmental absorption and transit (CAT) model to estimate saturable small intestinal absorption. This model simultaneously considers passive absorption, saturable absorption, degradation, and transit kinetics in the human small intestine. Using cefatrizine as a model drug, we demonstrated that the extended CAT model, along with intravenous pharmacokinetic parameters, was able to explain the observed oral plasma concentration-time profiles. The model predicted comparable passive and saturable absorption characteristics for cefatrizine, particularly at high dose. The predicted fraction of dose absorbed was 74% at 250 mg, 61% at 500 mg, and 48% at 1000 mg, in agreement with the reported experimental data. The simulation study showed that no single physiological factor (gastric emptying, small intestinal transit, and absorption mechanism) could account for the large variability of cefatrizine absorption observed in the literature.
本报告描述了一种扩展的房室吸收与转运（CAT）模型，用于估计小肠的饱和吸收。该模型同时考虑了人体小肠中的被动吸收、饱和吸收、降解和转运动力学。以头孢曲嗪为模型药物，我们证明扩展的CAT模型与静脉药代动力学参数一起，能够解释观察到的口服血浆浓度-时间曲线。该模型预测了头孢曲嗪类似的被动和饱和吸收特征，尤其是在高剂量时。预测的吸收剂量分数在250mg时为74%，在500mg时为61%，在1000mg时为48%，与报道的实验数据一致。模拟研究表明，没有单一的生理因素（胃排空、小肠转运和吸收机制）能够解释文献中观察到的头孢曲嗪吸收的巨大变异性。
