ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability

Autor: Klaus D. Wutzke, Frans Stellaard, Herman J. Woerdenbag, Jos G. W. Kosterink, H. M. van Rieke, R.C.A. Schellekens, Gerard Dijkstra, J.M. Maurer, Henderik W. Frijlink, D. J. Buurman
Přispěvatelé: Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Pharmaceutical Technology and Biopharmacy, Targeted Gynaecologic Oncology (TARGON), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Organ Transplantation (GIOT)
Rok vydání: 2013
Předmět:
Male
Food intake
food intake
Bioavailability
breathing
urinalysis
Pharmaceutical Science
Administration
Oral
meal
Urine
Pharmacology
Gastroenterology
Dosage form
Eating
Drug Delivery Systems
Crohn Disease
Food-interaction
stable isotope
Urea
drug release
Crohn's disease
Meal
clinical article
Cross-Over Studies
medicine.diagnostic_test
digestive
oral
and skin physiology
article
Middle Aged
priority journal
Female
Tablets
Enteric-Coated
Adult
medicine.medical_specialty
crossover procedure
Urinalysis
Adolescent
Colon
Stable-isotope
Biological Availability
Bioequivalence
in vivo study
urea c 13
Young Adult
remission
Ileum
Internal medicine
medicine
Humans
controlled study
nitrogen 15
human
isotope analysis
bioequivalence
tablet
business.industry
drug bioavailability
medicine.disease
Food
Delayed-Action Preparations
business
intestine transit time
Colon-delivery
Zdroj: Journal of controlled release : official journal of the Controlled Release Society, 172(3), 618-624. Elsevier Bedrijfsinformatie b.v.
ISSN: 1873-4995
Popis: ColoPulse tablets are an innovative development in the field of oral drug delivery and are characterized by a colon-specific release. Until now ColoPulse dosage forms (only capsules) have been studied in healthy volunteers having a standardized breakfast three hours after administration but not in specific patient groups and not with a shorter interval between administration and breakfast. Information on bioavailability and release characteristics of ColoPulse tablets in Crohn's patients and the influence of food and time of food intake is a prerequisite to properly design future clinical studies with active substances in these patients.In the current cross-over study bioavailability and drug release characteristics of ColoPulse tablets were compared in healthy volunteers and in Crohn's patients in remission. Furthermore the influence of food and time of food intake on the in vivo drug release behavior of ColoPulse tablets was investigated.In this study the dual label isotope strategy was used which means that a ColoPulse tablet containing C-13-urea and an uncoated, immediate release tablet containing N-15(2)-urea were taken simultaneously. Breath and urine samples were collected during the test day for isotope analysis. The appearance of the stable isotopes in breath and/or urine provides information on the site of release from the dosage form, release characteristics and bioavailability.Both tablets were administered on two different days in a cross-over design: the first day with a breakfast (non-standardized) one hour after administration and the second day with a standardized breakfast three hours after administration of the tablets. There was no difference in instructions for administration between both days.Results of 16 healthy volunteers and 14 Crohn's patients were evaluated. At least 86% (51 out of 59) of all ColoPulse tablets administered in this study released their contents at the desired intestinal region. There was no significant difference in bioavailability between healthy volunteers and Crohn's patients on both days (day 1 75.8% vs 90.2%, p = 0.070 and day 2 83.4% vs 91.4%, p = 0.265). There was also no significant influence of food and time of food intake on bioavailability in healthy volunteers (75.8% and 83.4%, p = 0.077) and in Crohn's patients (90.2% and 91.4%, p = 0.618) when day 1 and day 2 were compared. Release characteristics did not significantly differ between healthy volunteers and Crohn's patients. However, food and time of food intake had some, clinically non-relevant, influence on the release characteristics within both groups which is in line with the fact that food affects gastrointestinal transit times.This study shows that ColoPulse tablets enable the site-specific delivery of drugs or other compounds (e. g. diagnostics) deep in the ileo-colonic region of the intestine of Crohn's patients in a comparable amount and rate as in healthy volunteers. Food and time of food intake had no relevant influence on bioavailability. In conclusion ColoPulse delivery systems are promising and deserve further research for local therapy with immunosuppressive drugs in Crohn's patients in the near future. (C) 2013 Elsevier B.V. All rights reserved.
Databáze: OpenAIRE
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