alx-0600 and Liver-Diseases

In children, short-bowel syndrome (SBS) accounts for two-thirds of the cases of intestinal failure, and motility disorders and congenital mucosal diarrheal disorders account for the remaining one-third. Children with SBS are supported primarily by parenteral nutrition, which is the single-most important therapy contributing to their improved prognosis. More than 90% of children with SBS who are cared for at experienced intestinal rehabilitation programs survive, and roughly 60% to 70% undergo intestinal adaptation and achieve full enteral autonomy. This article focuses on the predictors of pediatric intestinal adaptation and discusses the pathophysiology and clinical management of children with SBS.

Topics: Adaptation, Physiological; Bacteremia; Biomarkers; Catheterization, Central Venous; Child; Citrulline; Enteral Nutrition; Gastrointestinal Agents; Humans; Liver Diseases; Parenteral Nutrition; Peptides; Prognosis; Short Bowel Syndrome

Teduglutide is a GLP-2 analog currently evaluated for the treatment of short bowel syndrome, Crohn's disease, and other gastrointestinal disorders. The population pharmacokinetics (PK) of teduglutide were assessed following daily subcutaneous (SC) administrations of 2.5 to 80 mg doses in a total of 256 patients. A 1-compartment model with a site-specific rate constant of absorption in the abdomen, arm, and thigh was used to assess the PK of teduglutide. Apparent clearance (CL/F) of teduglutide in male participants was approximately 18% higher than that observed in female participants (12.4 vs 10.5 L/h, respectively). Body weight was detected as a significant covariate explaining the volume of distribution of teduglutide. The elimination half-life (t((1/2))) of teduglutide was also influenced by the body weight of participants. For a male patient weighing 50 and 90 kg, t((1/2)) of teduglutide was 0.897 and 2.99 hours, respectively. Renal and hepatic function of patients did not affect the PK of teduglutide. As a result, no dose adjustment was deemed necessary in patients with altered renal or liver function. The population PK model will help to support adequate drug labeling following SC administrations in patients and determine whether an individualized dosage is required.

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Crohn Disease; Dose-Response Relationship, Drug; Female; Gastrointestinal Agents; Humans; Injections, Subcutaneous; Kidney Diseases; Liver Diseases; Male; Middle Aged; Models, Statistical; Peptides; Sex Characteristics; Short Bowel Syndrome

Short bowel syndrome (SBS) is an increasingly common condition encountered across neonatal intensive care units. Improvements in parenteral nutrition (PN), neonatal intensive care and surgical techniques, in addition to an improved understanding of SBS pathophysiology, have contributed in equal parts to the survival of this fragile subset of infants. Prevention of intestinal failure associated liver disease (IFALD) and promotion of intestinal adaptation are primary goals of all involved in the care of these patients. While enteral nutritional and pharmacological strategies are necessary to achieve these goals, there remains great variability in the application of therapeutic strategies in units that are not necessarily evidence-based.. A search of major English language medical databases (SCOPUS, Index Medicus, Medline, and the Cochrane database) was conducted for the key words short bowel syndrome, medical management, nutritional management and intestinal adaptation. All pharmacological and nutritional agents encountered in the literature search were classified based on their effects on absorptive capacity, intestinal adaptation and bowel motility that are the three major strategies employed in the management of SBS. The Oxford Center for Evidence-Based Medicine (CEBM) classification for levels of evidence was used to develop grades of clinical recommendation for each variable studied.. We reviewed various medications used and nutritional strategies included soluble fiber, enteral fat, glutamine, probiotics and sodium supplementation. Most interventions have scientific rationale but little evidence to support their role in the management of infant SBS. While some of these agents symptomatically improve diarrhea, they can adversely influence pancreatico-biliary function or actually impair intestinal adaptation. Surgical anatomy and liver function are two important variables that should determine the selection of pharmacological and nutritional interventions.. There is a paucity of research investigating optimal clinical practice in infant SBS and the little evidence available is consistently of lower quality, resulting in a wide variation of clinical practices among NICUs. Prospective trials should be encouraged to bridge the evidence gap between research and clinical practice to promote further progress in the field.

Topics: Atrophy; Case-Control Studies; Cohort Studies; Combined Modality Therapy; Critical Care; Diarrhea, Infantile; Dietary Fats; Dietary Fiber; Enteral Nutrition; Evidence-Based Medicine; Exocrine Pancreatic Insufficiency; Food, Formulated; Gastrointestinal Agents; Gastrointestinal Hormones; Gastrointestinal Motility; Glutamine; Humans; Infant; Infant Food; Infant, Newborn; Intensive Care Units, Neonatal; Liver Diseases; Pancreas, Exocrine; Pancreatic Extracts; Parenteral Nutrition; Peptides; Probiotics; Randomized Controlled Trials as Topic; Short Bowel Syndrome