Tumor necrosis factor-mediated disposition of infliximab in ulcerative colitis patients

AbstractUlcerative Colitis (UC) is an inflammatory bowel disease typically affecting the colon. Patients with active UC have elevated tumor necrosis factor (TNF) concentrations in serum and colonic tissue. Infliximab is a monoclonal antibody directed against TNF and binds with high affinity. Target-mediated drug disposition (TMDD) is reported for monoclonal antibodies meaning that their pharmacokinetics are affected by high target affinity. Here, a TMDD model is proposed to describe the interaction between infliximab and TNF in UC patients. Data from 20 patients with moderate to severe UC was used. Patients received standard infliximab induction therapy (5  mg kg−1) at week 0, followed by infusions at week 2 and 6. IFX, anti-drug antibodies and TNF serum concentrations were measured at day 0 (1  h after infusion), 1, 4, 7, 11, 14, 18, 21, 28 and 42. A binding model, TMDD model, and a quasi-steady state (QSS) approximation were evaluated using nonlinear mixed effects modeling (NONMEM). A two-compartment model best described the concentration–time profiles of infliximab. Typical clearance of infliximab was 0.404 L day−1 and increased with the presence of anti-drug antibodies and with lower albumin concentrations. The TMDD-QSS model best described the pharmacokinetic and pharmacodynamics data. Estimate for TNF baseline (Bmax was 19.8  pg mL−1 and the dissociation constant (Kss) was 13.6  nM. This model could eventually b...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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This study utilised 5-FU-treatment in a model of colitis-associated CRC to develop a pre-clinical setting of intestinal mucositis coincident with manifestation of CRC.Materials/methods: On day 0, female C57BL/6 mice (n = 10/group); (1) saline control, (2) AOM/DSS control, or (3) AOM/DSS + 5-FU were injected with saline or AOM (i.p; 7.4 mg/kg). Groups 2 and 3 underwent cycles of seven days 2%w/v DSS followed by 14 days plain water. After three cycles, 5-FU was administered weekly (i.p; 75 mg/kg) to group 3 for five weeks. Clinical indicators were measured daily and colonoscopy performed at...
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
CONCLUSIONS: this first systematic review published in the literature on this issue suggests that vedolizumab has significant efficacy in chronic refractory or antibiotic-dependent pouchitis, also in patients who failed to respond to other treatments including those with anti-TNF agents. PMID: 31823641 [PubMed - as supplied by publisher]
Source: Revista Espanola de Enfermedades Digestivas - Category: Gastroenterology Tags: Rev Esp Enferm Dig Source Type: research
Conclusion: All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in Scutellaria baicalensis (Tiaoqin) should be preferred in treatment of UC.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
THURSDAY, Dec. 12, 2019 -- From 1999 to 2017, the hospitalization rate for Crohn disease and ulcerative colitis decreased among non-Hispanic white Medicare beneficiaries aged ≥65 years, but not among non-Hispanic blacks, according to research...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
December 12, 2019 - Pfizer Inc. (NYSE:PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved Xeljanz XR (tofacitinib) extended-release 11 mg and 22 mg tablets for the once-daily treatment of adult patients with moderately...
Source: Drugs.com - New Drug Approvals - Category: Drugs & Pharmacology Source Type: news
THE EFFECT OF DAILY PHYSICAL ACTIVITY ON THE ACTIVITY OF INFLAMMATORY BOWEL DISEASES IN THERAPY-FREE PATIENTS. Acta Clin Croat. 2019 Jun;58(2):202-212 Authors: Holik D, Včev A, Milostić-Srb A, Salinger Ž, Ivanišević Z, Včev I, Miškulin M Abstract It has been suggested that various environmental factors play a very important role in the etiology of inflammatory bowel diseases (IBDs) and that they have a significant effect on the course of these diseases. The aim of this study was to investigate the effect of daily physical activity on the activity of IBDs in therapy-free patients. Thi...
Source: Acta Clinica Croatica - Category: General Medicine Tags: Acta Clin Croat Source Type: research
Conclusions: Colorectal stricture had the highest risk for malignant transformation. Earlier initiation of colonoscopic surveillance in UC patients with risk factors for stricture should be considered to prevent stricture formation and further malignant transformation. PMID: 31816674 [PubMed - as supplied by publisher]
Source: Gut and Liver - Category: Gastroenterology Tags: Gut Liver Source Type: research
Chronic inflammatory bowel diseases, such as Crohn's Disease and ulcerative colitis, are linked to abnormalities of the gut microbiota in humans and in animals. Patients generally present reduced bacterial diversity in their intestinal flora along with excessive levels of bacteria that express a protein called flagellin, which favors their mobility.
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured Research Research and Development Source Type: news
CONCLUSION: Our findings indicated that AS II could alleviate inflammatory response in LPS-induced CCD-18Co cells and in DSS-induced UC in mice. In conclusion, AS II may serve as a potential agent for the treatment of UC. PMID: 31814910 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
AbstractBackgroundUlcerative colitis frequently requires surgery as a definitive management strategy. The colonic specimen can be extracted from various sites including a midline incision, the stoma site, or a Pfannenstiel incision. It is unclear if one extraction site offers improved outcomes and fewer complications.MethodsA retrospective review of charts obtained of colorectal surgery patients was conducted for all patients with ulcerative colitis who underwent a subtotal colectomy between 2008 and 2016 at a single tertiary care institution. Demographic data and outcomes data including parastomal and incisional hernias, ...
Source: Journal of Gastrointestinal Surgery - Category: Surgery Source Type: research
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