title: Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants.
abstract: Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i.v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean 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 evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.
authors.affiliation: Department of Clinical Chemistry, Saint Luc University Hospital, Brussels, Belgium.
authors.forename: P E
authors.initials: PE
authors.lastname: Wallemacq
authors.forename: R
authors.initials: R
authors.lastname: Reding
authors.forename: E M
authors.initials: EM
authors.lastname: Sokal
authors.forename: J
authors.initials: J
authors.lastname: de Ville de Goyet
authors.forename: S
authors.initials: S
authors.lastname: Clement de Clety
authors.forename: V
authors.initials: V
authors.lastname: Van Leeuw
authors.forename: M
authors.initials: M
authors.lastname: De Backer
authors.forename: J B
authors.initials: JB
authors.lastname: Otte
mesh_terms: D000284:Administration, Oral; D002675:Child, Preschool; D002779:Cholestasis / Q000209:etiology; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003967:Diarrhea / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D015200:Fluoroimmunoassay; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007223:Infant; D016031:Liver Transplantation; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine