Mardini Houssam E, de Villiers Willem J S
University of Kentucky Chandler Medical Center, Division of Digestive Diseases and Nutrition, 800 Rose Street, Rm MN649, Lexington, KY 40536, USA.
Expert Opin Investig Drugs. 2008 Jun;17(6):945-51. doi: 10.1517/13543784.17.6.945.
Malabsorption of nutrients, fluids and electrolytes is a key finding in patients with short bowel syndrome. If not compensated for by increased intake, it leads to diminished body stores and subclinical, and eventually clinical, deficiencies. Until recently, management options were limited to interventions aimed at provision of adequate macro- and micronutrients and fluids to prevent malnutrition, nutrient deficiencies and dehydration, treatment of associated infections and correction and prevention of acid-base disturbances. Identification of novel gut hormones, combined with the growing understanding of their pivotal role in intestinal adaptation, has provoked interest in developing more specific therapies.
To provide an update on the recent advances on the use of teduglutide in patients with short bowel syndrome.
A comprehensive Medline search using the terms teduglutide, ALX-0600, dipeptidyl peptidase IV (DPP-IV) and glucagon like peptide-2 (GLP-2).
Teduglutide (GATTEX, ALX-0600; NPS Allelix Corp) is a synthetic DPP-IV-resistant recombinant human GLP-2 analog that differs from GLP-2 only by an N-terminus substitution of glycine for alanine in position 2 of the peptide that renders the component resistant to enzymatic degradation. Based on the results of the few Phase II studies and the preliminary results of a Phase III trial, teduglutide at doses of 0.05 or 0.10 mg/kg/day may improve many clinical, laboratory and histologic abnormalities in short bowel syndrome patients. It appears to be safe and well tolerated.
Teduglutide is a first-in-class therapy with the potential to create a new standard of care for patients suffering from short bowel syndrome. Future studies to address the appropriate initial and maintenance dosage and optimal duration of treatment are needed.
营养物质、液体和电解质吸收不良是短肠综合征患者的关键表现。若不通过增加摄入量来代偿，会导致身体储备减少，出现亚临床缺乏，最终发展为临床缺乏。直到最近，管理方案仍局限于旨在提供充足的宏量和微量营养素及液体以预防营养不良、营养缺乏和脱水，治疗相关感染以及纠正和预防酸碱平衡紊乱的干预措施。新型肠道激素的发现，以及对其在肠道适应中关键作用的日益了解，引发了人们对开发更具特异性疗法的兴趣。
提供关于替度鲁肽用于短肠综合征患者的最新研究进展。
使用替度鲁肽、ALX - 0600、二肽基肽酶IV（DPP - IV）和胰高血糖素样肽 - 2（GLP - 2）等检索词对Medline进行全面检索。
替度鲁肽（GATTEX，ALX - 0600；NPS Allelix公司）是一种合成的、对DPP - IV耐药的重组人GLP - 2类似物，与GLP - 2的区别仅在于肽链第2位的N端甘氨酸被丙氨酸取代，这使得该成分对酶降解具有抗性。基于少数II期研究结果和一项III期试验的初步结果，剂量为0.05或0.10mg/kg/天的替度鲁肽可能改善短肠综合征患者的许多临床、实验室和组织学异常。它似乎安全且耐受性良好。
替度鲁肽是一流的疗法，有可能为短肠综合征患者创造新的护理标准。需要进一步研究以确定合适的初始和维持剂量以及最佳治疗持续时间。
