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使用无线胶囊式内窥镜比较健康受试者和有症状便秘患者的小肠 pH 值和运动情况。

Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule.

机构信息

Small Molecule Design and Development, Lilly Research Labs, Eli Lilly & Company, Indianapolis, IN, United States.

Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, IN, United States.

出版信息

Int J Pharm. 2018 Jun 10;544(1):158-164. doi: 10.1016/j.ijpharm.2018.04.031. Epub 2018 Apr 17.

Abstract

Gastrointestinal luminal pH shows a rise from the duodenum to the terminal ileum in healthy individuals. Our objectives were to compare the pH in the proximal small intestine (SI) (first 60 min of small intestinal transit) lumen of human volunteers and patients with symptomatic constipation; to quantify contractile pressure profiles of the proximal SI, and to assess the relationship between luminally-recorded contractile pressure and small intestinal transit times (SITT) of a non-disintegrating capsule that measures pH and pressure activity (wireless motility capsule). We used previously acquired records from 39 healthy subjects and 41 patients with symptomatic constipation. Mean pH (±SD) of the proximal SI was similar in healthy subjects and patients with constipation at 6.2 (±0.6) and 6.3 (±0.4), respectively. In 13 of the healthy subjects, pH did not rise uniformly in the proximal SI though the pH was 6.0 (5th, 95th percentiles 3.09, 7.06) and the pH fluctuated over a mean period of 28 min. Large inter-individual variability in frequency of pressure activity (Ct) and area under pressure curve (AUC) were observed in the proximal SI of healthy subjects and patients with constipation. Median AUC was 3996 mmHg s (5th, 95th percentiles 948, 16866 mmHg s) in these two populations combined. Ct and AUC showed a strong direct linear correlation at r = 0.91, p < 1 × 10. An inverse correlation (suggesting longer SITT with lower pressure activity) was observed between Ct/AUC and SITT in both healthy subjects and patients with symptomatic constipation. The pooled results for both groups showed: AUC and SITT correlation at r = -0.49, p < 1 × 10. We concluded that both the frequency and amplitude of contractions in the proximal SI are important for the propagation of non-disintegrating capsules. The observed pH fluctuations in the proximal SI may impact supersaturation and precipitation of weakly basic drugs.

摘要

健康个体的胃肠道腔 pH 值从十二指肠上升到末端回肠。我们的目的是比较健康志愿者和有症状便秘患者的近端小肠(SI)(小肠转运的前 60 分钟)腔内 pH 值;定量记录近端 SI 的收缩压力曲线,并评估无线动力胶囊(一种测量 pH 值和压力活动的非崩解胶囊)记录的腔内收缩压力与小肠转运时间(SITT)之间的关系。我们使用了 39 名健康受试者和 41 名有症状便秘患者的先前获得的记录。健康受试者和便秘患者近端 SI 的平均 pH 值(±SD)分别为 6.2(±0.6)和 6.3(±0.4)。在 13 名健康受试者中,尽管 pH 值为 6.0(5 分位,95 分位 3.09,7.06),且 pH 值波动持续平均 28 分钟,但近端 SI 的 pH 值并未均匀上升。健康受试者和便秘患者近端 SI 中的压力活动(Ct)和压力曲线下面积(AUC)的个体间变异性很大。这两个人群的 AUC 中位数为 3996mmHg·s(5 分位,95 分位 948,16866mmHg·s)。Ct 和 AUC 在 r=0.91 时呈强烈的直接线性相关,p<1×10。在健康受试者和有症状便秘患者中,Ct/AUC 与 SITT 之间观察到负相关(提示压力活动较低时 SITT 较长)。两组的合并结果显示:AUC 和 SITT 的相关性 r=-0.49,p<1×10。我们得出结论,近端 SI 中的收缩频率和幅度对非崩解胶囊的传播都很重要。近端 SI 中观察到的 pH 值波动可能会影响弱碱性药物的过饱和和沉淀。

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