Challenges in drug development for functional gastrointestinal disorders. Part I

Functional dyspepsia

V. Andresen, Michael Camilleri

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

There is a need to have predictive biomarkers to test novel experimental medicines in functional gastrointestinal disorders (FGID). The human pharmacodynamic models and biomarkers in functional dyspepsia (part I) and visceral pain (part II) are reviewed, including the general challenges of these two disorders (part I). Part II will also discuss the importance of drug pharmacokinetics and potential of pharmacogenomics, including the influence of CYP metabolism and potential drug interactions. The great heterogeneity of mechanisms potentially responsible for dyspeptic symptoms adds a significant complexity to this FGID. Strategies are needed to identify subgroups most likely to benefit from a specific pharmacological action targeted to one or more mechanisms. Thus, while there are significant challenges in drug development for functional dyspepsia, there is still an important role for pharmacodynamic studies. It remains to be demonstrated that identifying subgroups enhances the response to the pharmacological drug effect. This is feasible as the end points and performance of each test of gastric emptying, accommodation and sensitivity are well characterized. Of these, gastric emptying appears best validated at present, though responsiveness to this biomarker has not yet been translated into positive phase III trials. Eligibility criteria are proposed for selection of patients for functional dyspepsia trials.

Original languageEnglish (US)
Pages (from-to)346-353
Number of pages8
JournalNeurogastroenterology and Motility
Volume18
Issue number5
DOIs
StatePublished - May 2006

Fingerprint

Gastrointestinal Diseases
Dyspepsia
Biomarkers
Gastric Emptying
Patient Selection
Pharmaceutical Preparations
Pharmacology
Visceral Pain
Pharmacogenetics
Drug Interactions
Biomedical Research
Pharmacokinetics

Keywords

  • Biomarker
  • Clinical trial design
  • Gastric accommodation
  • Gastric emptying

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

Challenges in drug development for functional gastrointestinal disorders. Part I : Functional dyspepsia. / Andresen, V.; Camilleri, Michael.

In: Neurogastroenterology and Motility, Vol. 18, No. 5, 05.2006, p. 346-353.

Research output: Contribution to journalArticle

@article{4162a5098ed54e2d838a3f93df3c6554,
title = "Challenges in drug development for functional gastrointestinal disorders. Part I: Functional dyspepsia",
abstract = "There is a need to have predictive biomarkers to test novel experimental medicines in functional gastrointestinal disorders (FGID). The human pharmacodynamic models and biomarkers in functional dyspepsia (part I) and visceral pain (part II) are reviewed, including the general challenges of these two disorders (part I). Part II will also discuss the importance of drug pharmacokinetics and potential of pharmacogenomics, including the influence of CYP metabolism and potential drug interactions. The great heterogeneity of mechanisms potentially responsible for dyspeptic symptoms adds a significant complexity to this FGID. Strategies are needed to identify subgroups most likely to benefit from a specific pharmacological action targeted to one or more mechanisms. Thus, while there are significant challenges in drug development for functional dyspepsia, there is still an important role for pharmacodynamic studies. It remains to be demonstrated that identifying subgroups enhances the response to the pharmacological drug effect. This is feasible as the end points and performance of each test of gastric emptying, accommodation and sensitivity are well characterized. Of these, gastric emptying appears best validated at present, though responsiveness to this biomarker has not yet been translated into positive phase III trials. Eligibility criteria are proposed for selection of patients for functional dyspepsia trials.",
keywords = "Biomarker, Clinical trial design, Gastric accommodation, Gastric emptying",
author = "V. Andresen and Michael Camilleri",
year = "2006",
month = "5",
doi = "10.1111/j.1365-2982.2006.00778.x",
language = "English (US)",
volume = "18",
pages = "346--353",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Challenges in drug development for functional gastrointestinal disorders. Part I

T2 - Functional dyspepsia

AU - Andresen, V.

AU - Camilleri, Michael

PY - 2006/5

Y1 - 2006/5

N2 - There is a need to have predictive biomarkers to test novel experimental medicines in functional gastrointestinal disorders (FGID). The human pharmacodynamic models and biomarkers in functional dyspepsia (part I) and visceral pain (part II) are reviewed, including the general challenges of these two disorders (part I). Part II will also discuss the importance of drug pharmacokinetics and potential of pharmacogenomics, including the influence of CYP metabolism and potential drug interactions. The great heterogeneity of mechanisms potentially responsible for dyspeptic symptoms adds a significant complexity to this FGID. Strategies are needed to identify subgroups most likely to benefit from a specific pharmacological action targeted to one or more mechanisms. Thus, while there are significant challenges in drug development for functional dyspepsia, there is still an important role for pharmacodynamic studies. It remains to be demonstrated that identifying subgroups enhances the response to the pharmacological drug effect. This is feasible as the end points and performance of each test of gastric emptying, accommodation and sensitivity are well characterized. Of these, gastric emptying appears best validated at present, though responsiveness to this biomarker has not yet been translated into positive phase III trials. Eligibility criteria are proposed for selection of patients for functional dyspepsia trials.

AB - There is a need to have predictive biomarkers to test novel experimental medicines in functional gastrointestinal disorders (FGID). The human pharmacodynamic models and biomarkers in functional dyspepsia (part I) and visceral pain (part II) are reviewed, including the general challenges of these two disorders (part I). Part II will also discuss the importance of drug pharmacokinetics and potential of pharmacogenomics, including the influence of CYP metabolism and potential drug interactions. The great heterogeneity of mechanisms potentially responsible for dyspeptic symptoms adds a significant complexity to this FGID. Strategies are needed to identify subgroups most likely to benefit from a specific pharmacological action targeted to one or more mechanisms. Thus, while there are significant challenges in drug development for functional dyspepsia, there is still an important role for pharmacodynamic studies. It remains to be demonstrated that identifying subgroups enhances the response to the pharmacological drug effect. This is feasible as the end points and performance of each test of gastric emptying, accommodation and sensitivity are well characterized. Of these, gastric emptying appears best validated at present, though responsiveness to this biomarker has not yet been translated into positive phase III trials. Eligibility criteria are proposed for selection of patients for functional dyspepsia trials.

KW - Biomarker

KW - Clinical trial design

KW - Gastric accommodation

KW - Gastric emptying

UR - http://www.scopus.com/inward/record.url?scp=33645811289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645811289&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2982.2006.00778.x

DO - 10.1111/j.1365-2982.2006.00778.x

M3 - Article

VL - 18

SP - 346

EP - 353

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

IS - 5

ER -