THERAPEUTIC DRUG-MONITORING OF TACROLIMUS IN CLINICAL TRANSPLANTATION

Initial clinical trials of FK did not incorporate available FK levels, and difficulties were quickly experienced particularly with neurotoxi city and nephrotoxicity. The introduction of routine assay allowed bro ad parameters to be identified, which assisted in evaluating effective therapeutic parameters. Levels similar to 20 ng/ml were frequently as sociated with toxicity and the initial therapeutic range between 10-25 ng/ml was probably excessive. Reliable effective assay >5 ng/ml using the Abbott IM, is not available, and many patients will have excellen t hepatic or renal function with what are currently undetectable level s of FK. However, IncStar have an ELISA assay with a sensitivity of 0. 5 mg/ml. Clinical practice does not, at this time, dictate elevation o f FK, although careful monitoring continues. Education of oral adminis tration from 0.15 mg/kg to 0.1 mg/kg in combination therapy with stero ids and 0.05 mg/kg with azathioprine and steroids has led to revision of therapeutic parameters, e.g., 5-15 ng/ml is now widely used. Therap eutic drug monitoring is important to avoid unnecessary toxicity, but the lower limit has not been fully defined. Clearly, many patients wit h <5 ng/ml have excellent hepatic function.