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lüll Therapeutic drug monitoring in patients with inflammatory bowel disease Yarur AJ; Abreu MT; Deshpande AR; Kerman DH; Sussman DAWorld J Gastroenterol 2014[Apr]; 20 (13): 3475-84Thiopurine analogs and anti-tumor necrosis factor (TNF) agents have dramatically changed the therapeutics of inflammatory bowel diseases (IBD), improving short and long-term outcomes. Unfortunately some patients do not respond to therapy and others lose response over time. The pharmacokinetic properties of these drugs are complex, with high inter-patient variability. Thiopurine analogs are metabolized through a series of pathways, which vary according to the patients' pharmacogenetic profile. This profile largely determines the ratios of metabolites, which are in turn associated with likelihoods of clinical efficacy and/or toxicity. Understanding these mechanisms allows for manipulation of drug dose, aiming to reduce the development of toxicity while improving the efficacy of treatment. The efficacy of anti-TNF drugs is influenced by many pharmacodynamic variables. Several factors may alter drug clearance, including the concomitant use of immunomodulators (thiopurine analogs and methotrexate), systemic inflammation, the presence of anti-drug antibodies, and body mass. The treatment of IBD has evolved with the understanding of the pharmacologic profiles of immunomodulating and TNF-inhibiting medications, with good evidence for improvement in patient outcomes observed when measuring metabolic pathway indices. The role of routine measurement of metabolite/drug levels and antibodies warrants further prospective studies as we enter the era of personalized IBD care.|Adalimumab[MESH]|Antibodies, Monoclonal, Humanized/administration & dosage[MESH]|Antibodies, Monoclonal/administration & dosage[MESH]|Antibodies/administration & dosage[MESH]|Azathioprine/administration & dosage[MESH]|Drug Monitoring/*methods[MESH]|Genotype[MESH]|Humans[MESH]|Immunologic Factors[MESH]|Inflammation[MESH]|Inflammatory Bowel Diseases/*drug therapy[MESH]|Infliximab[MESH]|Methyltransferases/genetics[MESH]|Phenotype[MESH]|Purines/chemistry[MESH]|Thioguanine/administration & dosage[MESH]|Thionucleosides/chemistry[MESH]|Treatment Outcome[MESH]|Tumor Necrosis Factor-alpha/antagonists & inhibitors[MESH] |