MEASUREMENT OF TACROLIMUS (FK506) AND ITS METABOLITES - A REVIEW OF ASSAY DEVELOPMENT AND APPLICATION IN THERAPEUTIC DRUG-MONITORING AND PHARMACOKINETIC STUDIES

Tacrolimus (FK506, Prograf) is a macrolide immunosuppressant used for the prevention of organ rejection after transplantation. Tacrolimus de monstrates considerable interindividual variation in its pharmacokinet ic 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 specim ens have been developed. These assay methods were used for therapeutic drug monitoring and/or pharmacokinetic studies, Two commercially avai lable immunoassays. based on the same monoclonal antibody to tacrolimu s, have been used for therapeutic drug monitoring of tacrolimus in who le blood. For pharmacokinetic studies, the assay methods were used to measure tacrolimus and its metabolites in very low concentrations in s elected biological matrixes to determine the metabolic and pharmacokin etic profiles of this drug.