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

A. Aburub, M. Fischer, Michael Camilleri, J. R. Semler, H. M. Fadda

Research output: Contribution to journalArticle

9 Scopus citations

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 pHmedian 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−1 (5th, 95th percentiles 948, 16866 mmHg s−1) in these two populations combined. Ct and AUC showed a strong direct linear correlation at r = 0.91, p < 1 × 10−6. 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 × 10−6. 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.

Original languageEnglish (US)
Pages (from-to)158-164
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume544
Issue number1
DOIs
StatePublished - Jun 10 2018

Keywords

  • Absorption
  • Bioavailability
  • Disintegration
  • Dissolution
  • Enteric
  • Modified release

ASJC Scopus subject areas

  • Pharmaceutical Science

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