Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran.
Expert Opin Drug Metab Toxicol. 2013 Apr;9(4):403-21. doi: 10.1517/17425255.2013.759558. Epub 2013 Jan 19.
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.
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.
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.
肠易激综合征（IBS）是一种常见的慢性胃肠道（GI）疾病，其患病率较高，且目前尚无满意的有效药物，其复杂的病理生理学导致了对新治疗药物的需求。在新药开发过程中，药代动力学特征与药物疗效同样重要。这涉及到药物的吸收、分布、代谢和排泄，所有这些都是药物有效性的关键。此外，还应确定药物的毒理学特征和可能的不良反应。还应在不同的试验阶段确定其相互作用。进行了几项药代动力学研究，以获得具有最佳吸收和生物利用度、最小不良反应和最低毒性的药物。
为了更新用于 IBS 的新临床引入药物及其动态和动力学数据，进行了本系统综述。从 2003 年到 2012 年 5 月，搜索了所有相关的文献数据库，以确定评估新型药物在 IBS 中潜在疗效的所有临床试验。
一些评估药物，如雷莫司琼（5-HT3 拮抗剂）和pexacerfont（CRF1 受体拮抗剂），在腹泻型 IBS（D-IBS）中显示出一些益处，而普芦卡必利和莫沙必利（5-HT4 激动剂）具有促动力作用，在便秘型 IBS（C-IBS）中被发现有用。此外，dexloxiglumide、lubiprostone 和 linaclotide 对 C-IBS 患者有有益的影响。褪黑素调节胃肠道蠕动，asimadoline、加巴喷丁和普瑞巴林可降低疼痛阈值和内脏高敏性。胰高血糖素样肽类似物、钙通道阻滞剂和神经激肽受体拮抗剂在疼痛发作时显示出益处。由于多因素病理生理学、个体反应的变化和评估方法不足，长期治疗的疗效和安全性需要更多的时间来确定，这限制了对这些新药疗效和耐受性的正确决策过程。
