A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption-Part I: Gastrointestinal pH
A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption-Part I: Gastrointestinal pH
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DOI：
10.1208/s12248-016-9952-8
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发表时间：
2016-09-01
期刊：
影响因子：
4.5
通讯作者：
Upton, Richard N.
中科院分区：
文献类型：
--
作者：
Abuhelwa, Ahmad Y.;Foster, David J. R.;Upton, Richard N.
本研究旨在对不同GI段的胃肠道（GI）pH值和变异性进行定量荟萃分析;表征食物对这些参数值和变异性的影响;并提出GI pH分布的定量荟萃模型，以帮助为口服药物吸收模型提供信息。对进食和空腹条件下GI pH值及其变异性的文献进行了系统综述。胃肠道分为以下10个不同区域：胃（近端、中远端）、十二指肠（近端、中远端）、空肠和回肠（近端、中间和远端小肠）以及结肠（升结肠、横结肠和降结肠）。Meta分析使用R语言的“metafor”包。使用NONMEM对餐后胃pH的时间过程进行建模。食物显着影响估计元平均胃和十二指肠pH值，但没有显着影响小肠和结肠pH值。使用指数模型描述的时间过程餐后pH值。增加膳食热量增加的程度和持续时间的餐后胃pH值缓冲。小肠的不同部位有显着不同的pH值。结肠pH值显着不同的降结肠，但不为升结肠和横结肠。了解GI pH值对于pH依赖性剂型的处方设计以及了解口服药物的溶出度和吸收非常重要。GI pH的元模型也可用作半生理药代动力学模型的一部分，以表征GI pH对体内药物释放和药代动力学的影响。
This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) pH in the different GI segments; characterize the effect of food on the values and variability in these parameters; and present quantitative meta-models of distributions of GI pH to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, GI pH under fed and fasted conditions. The GI tract was categorized into the following 10 distinct regions: stomach (proximal, mid-distal), duodenum (proximal, mid-distal), jejunum and ileum (proximal, mid, and distal small intestine), and colon (ascending, transverse, and descending colon). Meta-analysis used the "metafor" package of the R language. The time course of postprandial stomach pH was modeled using NONMEM. Food significantly influenced the estimated meta-mean stomach and duodenal pH but had no significant influence on small intestinal and colonic pH. The time course of postprandial pH was described using an exponential model. Increased meal caloric content increased the extent and duration of postprandial gastric pH buffering. The different parts of the small intestine had significantly different pH. Colonic pH was significantly different for descending but not for ascending and transverse colon. Knowledge of GI pH is important for the formulation design of the pH-dependent dosage forms and in understanding the dissolution and absorption of orally administered drugs. The meta-models of GI pH may also be used as part of semi-physiological pharmacokinetic models to characterize the effect of GI pH on the in vivo drug release and pharmacokinetics.