Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients

The relationship between the dose of tacrolimus, trough tacrolimus blood co ncentration, and selected clinical endpoints (acute rejection, nephrotoxici ty, and other toxicities) were examined in a prospective, multicenter clini cal trial to validate the use of an enzyme-linked immunosorbent assay (ELIS A) for monitoring whole-blood concentrations of tacrolimus in liver transpl ant patients. A total of 111 subjects from six transplant centers were eval uated over 12 weeks posttransplantation. In addition to trough tacrolimus b lood concentrations, hematocrit, ALT, AST, GGTP, alkaline phosphatase, tota l bilirubin, serum creatinine, BUN, serum potassium, serum magnesium, blood glucose, and serum albumin were also measured. The relationship between tr ough tacrolimus blood concentrations and clinical endpoints was analyzed us ing both a logistic regression model and a Cox proportional hazard model. B y logistic regression analysis, a statistically significant (p = 0.0465) re lationship between increasing trough tacrolimus blood concentrations and de -creasing risk of acute rejection was demonstrated over a 7-day time window . Nephrotoxicity and other toxicities also demonstrated statistically signi ficant relationships with trough tacrolimus blood concentrations. The resul ts of the Cox analysis were consistent with the logistic regression analysi s. Using receiver operator characteristic curves, trough tacrolimus concent rations as measured by the ELISA method were able to differentiate the occu rrence of nephrotoxicity and toxicity from nonevents. To minimize nephrotox icity of tacrolimus, it is necessary to maintain trough blood concentration s below 15 ng/ml. This study demonstrates that the ELISA method used to mea sure tacrolimus blood concentrations in this study provides information of predictive value for managing the risk of nephrotoxicity, other toxicity, a nd rejection in liver transplant patients. (C) 2001 the American College of Clinical Pharmacology.