CLINICAL PHARMACOKINETICS OF NEORAL IN PEDIATRIC RECIPIENTS OF PRIMARY LIVER-TRANSPLANTS

Pediatric liver transplant recipients constitute a population characte rized by a particularly unpredictable and poor bioavailability of cycl osporin (CyA). Even though several adult studies show that the new ora l formulation of CyA, Neoral (NEO), produces better bioavailability an d blood level predictability, few data describe its pharmacokinetics i n children. We performed a complete analysis of the pharmacokinetics o f NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests ta ken during i.v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The me an half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22 % and 21 % for the first and last NEO doses . A large interpatient variability was observed. This was due, in part , to episodes of diarrhea that interfered with the pharmacokinetic eva luation and, in part, to the variability of post-transplant hepatic fu nction. There was a good correlation between CyA trough levels and the ir related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respecti vely). We conclude that, even though the pediatric OLT population rema ins more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.