The presence of fat in the gastric environment can affect the pharmacokinetic behaviour of drugs with mechanisms which have not been yet fully understood. The objective of the current study was to assess the drug partition to the lipid part of the fed gastric content under different emulsification conditions, using in vitro discriminating setups. The model drugs used in the study were selected on the basis of different physicochemical properties (lipophilicity, ionization, molecular weight and aqueous solubility) and different food effect observed in in vivo human studies. Fed State Simulated Gastric Fluid prepared with skimmed milk (FeSSGFsk) and anhydrous milk fat were used as surrogates for the aqueous and fat portions of the fed gastric environment respectively. An optimized biphasic model was developed so as to predict the differences in partition rate constants to fat, for model drugs of a wide range of the properties mentioned above. The experimental data and the use of statistical analysis revealed that molecular weight, molecular weight and log D pH 5 interaction and negative food effect act as negative factors to the rate constants of fat partition, while absence of food effect and logD pH 5 interaction with aqueous solubility affect the rate constants of partition to fat favourably.

中文翻译：

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根据药物特性研究在模拟进食状态下胃部条件下脂肪对脂肪的药物分配动力学。

胃环境中脂肪的存在会影响药物的药代动力学行为，其机理尚不完全清楚。本研究的目的是使用体外区分设置，评估在不同乳化条件下药物在进食胃内容物中脂质部分的分配。根据在体内人体研究中观察到的不同理化特性（亲脂性，离子化，分子量和水溶性）和不同的食物效应，选择了用于研究的模型药物。用脱脂牛奶（FeSSGFsk）和无水乳脂制备的美联储模拟胃液分别用作进食胃环境中水和脂肪部分的替代物。针对具有上述广泛特性的模型药物，开发了一种优化的双相模型，以预测分配速率常数与脂肪之间的差异。实验数据和统计分析的使用表明，分子量，分子量和log D pH 5相互作用以及负面食物效应是脂肪分配速率常数的负面因素，而没有食物效应和logD pH 5与水的相互作用溶解度有利地影响分配给脂肪的速率常数。