title: Measurement of tacrolimus (FK506) and its metabolites: a review of assay development and application in therapeutic drug monitoring and pharmacokinetic studies.
abstract: Tacrolimus (FK506, Prograf) is a macrolide immunosuppressant used for the prevention of organ rejection after transplantation. Tacrolimus demonstrates considerable interindividual variation in its pharmacokinetic profile. This has caused difficulty in defining the optimum regimen and has highlighted the need for therapeutic drug monitoring. Several assay methods for the measurements of tacrolimus in biological specimens have been developed. These assay methods were used for therapeutic drug monitoring and/or pharmacokinetic studies. Two commercially available immunoassays, based on the same monoclonal antibody to tacrolimus, have been used for therapeutic drug monitoring of tacrolimus in whole blood. For pharmacokinetic studies, the assay methods were used to measure tacrolimus and its metabolites in very low concentrations in selected biological matrixes to determine the metabolic and pharmacokinetic profiles of this drug.
authors.affiliation: Fujisawa Research Institute of America, Inc., Northwestern University/Evanston Research Park, Illinois 60201-3135, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Alak
mesh_terms: D001681:Biological Assay; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004268:DNA-Binding Proteins / Q000378:metabolism; D003619:Dansyl Compounds; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006834:Hydrazines; D007166:Immunosuppressive Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D013058:Mass Spectrometry; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D016559:Tacrolimus / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D022021:Tacrolimus Binding Proteins
chemical_list: D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D006360:Heat-Shock Proteins; D006834:Hydrazines; D007166:Immunosuppressive Agents; C027913:dansyl hydrazine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus