title: Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
authors: Shilan
authors: S
authors: Mozaffari
authors: Shekoufeh
authors: S
authors: Nikfar
authors: Mohammad
authors: M
authors: Abdollahi
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D004043:Dietary Fiber / Q000627:therapeutic use; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D010276:Parasympatholytics / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019936:Probiotics; D016032:Randomized Controlled Trials as Topic
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D000928:Antidepressive Agents; D004043:Dietary Fiber; D004365:Drugs, Chinese Herbal; D010276:Parasympatholytics