DIFFERENCES IN ORAL FK506 DOSE REQUIREMENTS BETWEEN ADULT AND PEDIATRIC LIVER-TRANSPLANT PATIENTS

The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerf ield, IL) after liver transplantation has, to date, made no distinctio n between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were stud ied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v . Thereafter, doses were adjusted to achieve therapeutic FK506 serum l evels (0.53. 0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, an d liver function were assessed at monthly intervals on outpatient visi ts. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy wer e 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patient s. For each time period, pediatric patients required a significantly h igher dose of FK506 compared to adult patients (P < 0.001). The overal l mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day co mpared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4. 4 over the 1 year of follow-up. FK506 levels monitored at the same tim e points showed no significant differences at any month between pediat ric and adult patients. We conclude that the oral dose per kilogram pe r day of FK506 required to maintain similar FK506 levels is significan tly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantiall y more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.