Relationship among changes in hematocrit, albumin and corticosteroid dose on the disposition of tacrolimus during the first six months following renal transplantation.

Abstract

Tacrolimus is a macrolide immunosuppressant that is safe and effective for the prevention of rejection after kidney transplantation. The oral bioavailability of tacrolimus averages 20% to 25%; however, the inter-individual variability in this parameter is large. Because of the poor correlation of dose to blood concentration between patients, the variability in pharmacokinetics and a relatively narrow therapeutic window, therapeutic drug monitoring of tacrolimus trough whole blood concentrations must be a standard practice. The objective of this evaluation was to determine the relationship among changes in hematocrit, albumin, and corticosteroid dosing on the disposition of tacrolimus during 6 months of treatment in renal transplant recipients. Blood samples for the determination of trough tacrolimus concentrations were taken immediately prior to the morning dose, samples were collected according to the request of the attending physician. Clinical and dosage data were reviewed 6 months after transplantation. The analysis was conducted including 11 patients who were analyzed for hematocrit and albumin at the same time they are measured tacrolimus blood levels. The mean age was 25.3 years (range 17 to 41 years) 4 of the patients were female. Levels of tacrolimus, hematocrit and albumin over the first 24 weeks post-transplant were documented and the estimated relative clearance of tacrolimus were calculated. Statistical evaluation of the data indicates poor correlation between relative clearance and both hematocrit and albumin levels and the mean oral steroid dose. This observation is of clinical significance because dose adjustment may be required to maintain blood concentrations within thetherapeutic range in patients in whom hematocrit or albumin concentrations are changing.