Advances of molecular clinical pharmacology in gastroenterology and hepatology.
During developmental age, differences in pharmacodynamic reactions to several drugs may reflect polymorphisms of genes encoding drug-transporting proteins, receptors, drug targets, and gene products, whose disturbed activity sometimes plays an important role in certain diseases. Administration of drugs with a narrow therapeutic index may quite easily be associated with changes in pharmacokinetics and development of adverse drug reactions, which occasionally may cause fatalities. In such cases, polypragmasy and resulting drug interactions may enhance effects of changes in drug-metabolizing enzymes' activities. Phenotyping and genotyping of patients slowly are finding their place in some therapeutic regimens used in clinical gastroenterology and hepatology. At present, some assays to measure, for example, thiopurine S-methyltransferase activity are already commercially available. Polymorphisms of CYP450 enzymes, interleukins, and altered gene expression play an important role in some patients' various gastrointestinal tract and liver diseases. Herbal drugs also affect proinflammatory and antiinflammatory cytokine and nitric oxide balance in the body. Therapeutic use of recombined proteins, such as infliximab, natalizumab, onercept, humanized antibody to integrin α-4 β-7, or IFN-β in some large-bowel diseases increased therapeutic efficacy. IFN-α used in the patients with chronic hepatitis C improved cellular immunity in these subjects and exerted antiviral activity. Practical application of progress in pharmacogenetics, pharmacokinetics, pharmacodynamics, and use of bioproducts in novel therapeutic regimens has opened therapeutic frontiers and increased clinical safety.
Department of Social Pediatrics, Faculty of Health Sciences, University School of Medicine, Wroclaw, Poland. prandota@ak.am.wroc.pl
Joseph
J
Prandota
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D032083:Citrus paradisi / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005762:Gastroenterology / Q000639:trends; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008107:Liver Diseases / Q000188:drug therapy* / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010597:Pharmacogenetics; D028321:Plant Preparations / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D011110:Polymorphism, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D028321:Plant Preparations; D003577:Cytochrome P-450 Enzyme System; D008780:Methyltransferases; C022745:thiopurine methyltransferase