Abuhelwa Ahmad Y, Foster David J R, Upton Richard N
Australian Centre for Pharmacometrics and Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
AAPS J. 2016 Sep;18(5):1322-1333. doi: 10.1208/s12248-016-9953-7. Epub 2016 Jul 20.
This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) transit times of non-disintegrating single-unit ("tablet") and multiple-unit ("pellets/multi-unit tablet") solid dosage forms, characterize the effect of food on the values and variability in these parameters and present quantitative meta-models of the distributions of GI transit times in the respective GI regions to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, gastric, small intestinal and colonic transit times under fed and fasted conditions. Meta-analysis used the "metafor" package of the R language. Meta-models of GI transit were assumed to be log-normally distributed between the studied populations. Twenty-nine studies including 125 reported means and standard deviations were used in the meta-analysis. Caloric content of administered food increased variability and delayed the gastric transit of both pellets and tablets. Conversely, food caloric content reduced the variability but had no significant influence on the mean small intestinal transit time (SITT). Food had no significant effect on the transit time through the colon. The transit of pellets through the colon was significantly slower than that of single-unit tablets which is most likely related to their smaller size. GI transit times may influence the dissolution and absorption of oral drugs. The meta-models of GI transit times may be used as part of semi-physiological absorption models to characterize the influence of transit time on the dissolution, absorption and in vivo pharmacokinetic profiles of oral drugs.
本研究旨在对不可崩解的单单元（“片剂”）和多单元（“微丸/多单元片剂”）固体剂型的胃肠道（GI）转运时间值及其变异性进行定量荟萃分析，表征食物对这些参数值及其变异性的影响，并给出各GI区域GI转运时间分布的定量荟萃模型，以辅助口服药物吸收模型的构建。对有关进食和禁食条件下胃、小肠和结肠转运时间值及其变异性的文献进行了系统综述。荟萃分析使用了R语言的“metafor”软件包。假定GI转运的荟萃模型在研究人群之间呈对数正态分布。荟萃分析纳入了29项研究，其中125项报告了均值和标准差。所给予食物的热量含量增加了变异性，并延迟了微丸和片剂的胃转运。相反，食物热量含量降低了变异性，但对平均小肠转运时间（SITT）没有显著影响。食物对结肠转运时间没有显著影响。微丸通过结肠的转运明显慢于单单元片剂，这很可能与其较小的尺寸有关。GI转运时间可能会影响口服药物的溶解和吸收。GI转运时间的荟萃模型可作为半生理吸收模型的一部分，用于表征转运时间对口服药物溶解、吸收和体内药代动力学特征的影响。
