Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patients.

The clinical utility of tacrolimus monitoring in adults has been well documented. The present study compared tacrolimus monitoring in a pediatric population of 34 liver transplant patients in four US centers with an adult population of 111 patients in six US centers. Subjects (adult and pediatric) were evaluated, at defined intervals over 12 weeks post-transplantation (Tx), for tacrolimus trough concentrations and 12 additional laboratory chemistries. Pediatric patient and graft survival for the 12 weeks were 91% and 88%, respectively, as compared to 97% and 93%, respectively, for the adult population. The mean oral dosage of tacrolimus for pediatric patients was 0.13 +/- 0.1 mg/kg/day at week 1, increased to 0.30 +/- 0.3 mg/kg/day by week 3 and remained constant for the remainder of the study. These dosages were two- to three-fold higher than the dosage used in the adult population. In contrast, the mean whole-blood trough concentration, as determined by PRO-Tractrade mark II enzyme-linked immunosorbent assay (ELISA), decreased from 11.3 +/- 5.1 ng/mL at week 1 to 6.3 +/- 3.7 ng/mL by week 12 and was not significantly different from the trough concentration in adults. The incidence and distribution of the clinical end-points for the pediatric subjects (rejection, nephrotoxicity, death, re-Tx) were different from those observed in adults. The total percentage of pediatric subjects reaching any end-point was 74%, as compared to 54% in the adult population. These data indicate several differences between the adult and pediatric populations in their response to tacrolimus.