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Population pharmacokinetics of tacrolimus in children who receive cut-down or full liver transplants.

Abstract：

BACKGROUND:The aim of this study was to investigate the population pharmacokinetics of tacrolimus in pediatric liver transplant recipients and to identify factors that may explain pharmacokinetic variability. METHODS:Data were collected retrospectively from 35 children who received oral immunosuppressant therapy with tacrolimus. Maximum likelihood estimates were sought for the typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) with the program NONMEM. Factors screened for influence on the pharmacokinetic parameters were weight, age, gender, postoperative day, days since commencing tacrolimus therapy, transplant type (whole child liver or cut-down adult liver), liver function tests (bilirubin, alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT]), creatinine clearance, hematocrit, corticosteroid dose, and concurrent therapy with metabolic inducers and inhibitors of tacrolimus. RESULTS:No clear correlation existed between tacrolimus dosage and blood concentrations (r2=0.003). Transplant type, age, and liver function test values were the most important factors (P<0.01) that influenced the pharmacokinetics of tacrolimus. CL/F estimates were greater in whole liver recipients, decreased with increasing patient age and AST values, and increased with increasing GGT values. Average parameter estimates were CL/F=5.75 L/h (cut-down liver), CL/F=44 L/h (whole liver), and V/F=617 L. Marked intersubject variability (CV%=110% to 297%) and residual variability (CV%=42%) was observed. CONCLUSIONS:Pharmacokinetic information obtained in this study may assist physicians in making individualized dosage decisions in regard to tacrolimus in pediatric liver transplant recipients. Children who received a whole child's liver appeared to retain "pediatric" clearance, whereas those who received a cut-down adult liver had "adult" clearances (on average 7-fold less).

journal_name

Transplantation

journal_title

Transplantation

authors

Staatz CE,Taylor PJ,Lynch SV,Willis C,Charles BG,Tett SE

doi

10.1097/00007890-200109270-00013

subject

Has Abstract

pub_date

2001-09-27 00:00:00

pages

1056-61

issue

eissn

0041-1337

issn

1534-6080

journal_volume

pub_type

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Population pharmacokinetics of tacrolimus in children who receive cut-down or full liver transplants.