Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome

Abstract

Introduction: The high prevalence of irritable bowel syndrome (IBS), a chronic gastrointestinal (GI) disorder, its lack of satisfactory effective drugs and its complicated pathophysiology lead to the demand of new therapeutic agents. During a new drug development process, the pharmacokinetic profiling is of a great considerable importance comparable to drug's efficacy. This involves the drug's absorption, distribution, metabolism and excretion, all of which are crucial to its usefulness. In addition, the toxicological profile and possible adverse reactions of the drug should be identified. Also its interactions should be identified at different phases of trials. Several pharmacokinetic studies are carried out to achieve drugs with the best absorption and bioavailability and the least adverse effects and lowest toxicity.

Areas covered: To make an update on new clinically introduced drugs for IBS and their dynamics and kinetics data, the present systematic review was accomplished. All relevant bibliographic databases were searched from the year 2003 up to May 2012 to identify all clinical trials that evaluated the potential efficacy of a novel agent in IBS.

Expert opinion: Some evaluated drugs, such as ramosetron (5-HT3 antagonist) and pexacerfont (CRF1 receptor antagonist), have shown some benefits in diarrhea-predominant IBS (D-IBS), while, prucalopride and mosapride (5-HT4 agonist) with prokinetic effect were found useful in constipation-predominant IBS (C-IBS). Besides, dexloxiglumide, lubiprostone and linaclotide have shown beneficial effects in C-IBS patients. Melatonin regulates GI tract motility and, asimadoline, gabapentin and pregabalin show reduction of pain threshold and visceral hypersensitivity. Glucagon-like peptide analog, calcium-channel blockers and neurokinin receptor antagonists have shown benefits in pain attacks. More time is required to indicate both efficacy and safety in long-term treatment due to multifactorial pathophysiology, variations in individual responses and insufficient assessment methods, which limit the right decision-making process about the efficacy and tolerability of these new drugs.

Keywords::

• irritable bowel syndrome
• metabolic and toxicological considerations
• new drugs
• systematic review

Acknowledgment

This paper is the outcome of an in-house financially non-supported study upon an invitation of Expert Opinion on Drug Metabolism and Toxicology. Authors acknowledge support of Iran National Science Foundation (INSF).

Notes

This box summarizes key points contained in the article.