Dataset Information

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets.

ABSTRACT:

Introduction

ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.

Materials and methods

Release from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing 13C-urea and an uncoated, immediate release tablet containing 15N2-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.

Results

Full analysis could be performed in 12 subjects. Median bioavailability of 13C -urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of 13C) was 5:42 h (95% CI 5:18-6:18 h, range 2:36-6:36 h,) There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT) based on pH (median 5:42 vs 5:31 h p = 0.903). In all subjects an intestinal pH value of 7.0 was reached before release of 13C from the ColoPulse tablet occurred.

Discussion and conclusions

From the combined data from the IntelliCap system and the 13C -isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.

Trial registration

ISRCTN Registry 18301880.

SUBMITTER: Maurer JM

PROVIDER: S-EPMC4503763 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets.

Maurer Jacoba M JM Schellekens Reinout C A RC van Rieke Hèlen M HM Wanke Christoph C Iordanov Ventzeslav V Stellaard Frans F Wutzke Klaus D KD Dijkstra Gerard G van der Zee Margot M Woerdenbag Herman J HJ Frijlink Henderik W HW Kosterink Jos G W JG

PloS one 20150715 7

<h4>Introduction</h4>ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.<h4>Materials and methods</h4>Release from ColoPulse tablets was studied in 16 healthy ...[more]

PMID: 26177019

Similar Datasets

Project description:BACKGROUND: Stronger prokinetic agents which specifically enhance transit in different parts of the gut are required. R093877 is a novel 5-HT4 agonist prokinetic compound which is chemically related to cisapride but believed to have greater effect on colonic activity. AIMS: To evaluate the effects of R093877 on bowel function, upper and lower gut transit, visceral sensitivity, and sphincter function in healthy volunteers in a double blind, placebo controlled, crossover study. METHODS: The study consisted of five consecutive one week periods: no drug treatment; active drug treatment with either 1 or 2 mg daily or placebo; washout; active drug or placebo; no treatment. Seventeen male subjects maintained a detailed dairy of bowel function for the entire study. Orocaecal transit (breath hydrogen), whole gut transit (radio-opaque markers), and anorectal function were assessed at the end of each of the two treatment periods. Blood testing was performed to confirm compliance and for safety analysis. RESULTS: One subject withdrew from the study due to side effects while on placebo. Eight subjects completed the study on 1 mg and a further eight on 2 mg. Blood testing showed non-compliance in one subject on the 2 mg dose, and he was excluded from analysis of all diary and physiological data. Treatment increased the number of stools per week (placebo versus 1 mg, 7.8 versus 13.6, p = 0.003; placebo versus 2 mg, 8.9 versus 11.3, p = 0.15) and the percentage of loose or watery stools (24.2% versus 61.5%, p < 0.04; 9.9% versus 40.0%, p < 0.02). Stool frequency and consistency reverted to normal immediately after treatment. Treatment shortened orocaecal and whole gut transit in all subjects on both doses. Treatment accelerated orocaecal (76 versus 51 minutes, p = 0.007; 63 versus 47 minutes, p = 0.07) and whole gut (38.2 versus 27.0 hours, p = 0.05; 44.8 versus 24.0 hours, p < 0.04) transit, and decreased the number of retained markers ingested 36 hours previously (4.8 versus 1.8, p = 0.016; 7.0 versus 4.3, p = 0.033). Gut sensitivity to distension and electrical stimulation, and anal manometry, were unchanged. Transient headache occurred in seven subjects on R093877 and one subject had mild elevation of liver aminotransferases which resolved on drug cessation. CONCLUSIONS: R093877 is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and upper gut and colonic transit. It does not affect visceral sensitivity or sphincter function. It holds promise for patients with large bowel symptoms or slow gut transit.

Project description:BACKGROUND: Colonic motor function has not been studied in the ambulatory setting over a prolonged period in the unprepared state. Furthermore, the disturbance of this function in patients with faecal incontinence is unknown. AIM: To study colonic function over two to three days in the ambulatory, unprepared state in health and in patients with idiopathic faecal incontinence. METHODS: Six healthy women and six women with faecal incontinence and a structurally intact anal sphincter ingested a dual radioisotope meal, and had a six sensor, solid state manometric probe colonoscopically inserted into the left colon. Scanning was performed until radioisotope left the gut and pressure was recorded for a median of 44 hours. RESULTS: Three of six patients showed abnormal gastric emptying. Patients showed no disturbance of colonic radioisotope transit. Controls had a median of 12, whereas patients had a median of 16, high amplitude propagated waves per 24 hours. In three patients urge incontinence was associated with high amplitude (up to 500 cm water) propagated waves which often reached the rectum. These high pressure waves were identical to those occurring in healthy subjects, the only difference being the lack of adequate sphincter response. Passive incontinence was not associated with colonic motor activity. Defaecation in all subjects was associated with identical propagated waves, and distal movement of 13% (median) of right colonic content and excretion of 32% from the left colon and rectum. The urge to defaecate was associated with either propagated waves (45%) or non-propagated contractions (55%). Rectal motor complexes were recorded in both groups of subjects, but similar rhythmic activity was also recorded in the sigmoid and descending colon. CONCLUSIONS: Normal colonic function consists of frequent high pressure propagated waves. Rhythmic activity occurs both proximal to and in the rectum. Defaecation is characterised by high pressure propagated waves associated with coordinated anal sphincter relaxation. Patients with faecal incontinence may have a widespread disturbance of gut function. Urge incontinence, an urge to defaecate, and defaecation can all be associated with identical high amplitude propagated pressure waves.

Project description:Purpose:This study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and assesses the bioequivalence of the two products in healthy Chinese volunteers to obtain sufficient evidence for the marketing approval of the generic drug. Materials and Methods:A randomized, open-label, two-period crossover study (clinicaltrials.gov, NCT03646526) was conducted under both fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a single 25 mg dose of either the test or the reference formulation, followed by a 3-week washout period. Blood samples were collected until 144 h following administration. The pharmacokinetic parameters were acquired based on the concentration-time profiles, including the areas under the plasma concentration-time curve (AUC0-t, AUC0-?), the peak plasma concentration (Cmax), the time to achieve Cmax (Tmax), and the elimination half-life (t1/2). The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals (CIs) of amitriptyline were acquired for bioequivalence analysis, and values of these parameters for nortriptyline were used for comparison of therapeutic outcomes. Safety assessments included laboratory tests, physical examination, vital signs, and incidence of adverse events (AEs). Results:The values of t1/2 and Tmax for amitriptyline were not significantly different between the test and reference products under both fasting and fed conditions (P > 0.05). The GMRs of Cmax, AUC0-t, and AUC0-? between the two products, and corresponding 90% CIs, were all within the range of 80% to 125% under both fasting and fed conditions. The test and reference products were well tolerated and did not elicit serious adverse events. Conclusion:This study demonstrated that the generic and reference products were well tolerated by the subjects and bioequivalent, according to the rate and extent of the drug absorption.

Dataset Information

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets.

Introduction

Materials and methods

Results

Discussion and conclusions

Trial registration

Publications

Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets