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Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics Iwasaki KDrug Metab Pharmacokinet 2007[Oct]; 22 (5): 328-35Tacrolimus (FK506), an immunosuppressive drug, is co-medicated with multiple drugs under clinical conditions. Tacrolimus is highly lipophilic and is excreted from the body after receiving extensive metabolism. Due to its narrow therapeutic window following organ transplantation, tacrolimus requires therapeutic drug monitoring by an enzyme immunoassay using the monoclonal antibody raised against tacrolimus. Therefore, metabolism studies including drug-drug interaction and metabolite identification studies are essential for the efficient development and clinically optimal usage of this drug. Tacrolimus was metabolized by the cytochrome P450 (CYP) 3A subfamily. Metabolic drug-drug interaction studies were conducted to provide information regarding the optimal usage of tacrolimus, and its metabolism was inhibited by known CYP3A inhibitors such as ketoconazole, cyclosporine A, and nifedipine. Recent reports on clinical pharmacokinetics indicate that dose levels of tacrolimus need to be adjusted in transplant patients with CYP3A5 polymorphism.|Biotransformation[MESH]|Cyclosporine/pharmacology[MESH]|Cytochrome P-450 CYP3A Inhibitors[MESH]|Cytochrome P-450 CYP3A/genetics/*metabolism[MESH]|Cytochrome P-450 Enzyme System/metabolism[MESH]|Drug Interactions[MESH]|Drug Monitoring/methods[MESH]|Enzyme Inhibitors/pharmacology[MESH]|Humans[MESH]|Immunoenzyme Techniques[MESH]|Immunosuppressive Agents/blood/chemistry/*pharmacokinetics[MESH]|Ketoconazole/pharmacology[MESH]|Molecular Structure[MESH]|Nifedipine/pharmacology[MESH]|Polymorphism, Single Nucleotide[MESH]|Tacrolimus/blood/chemistry/*pharmacokinetics[MESH] |
