Population pharmacokinetics of tacrolimus in paediatric liver transplant recipientsWallin, Johan (Uppsala University, Division of Pharmacokinetics and Drug Therapy) (Pharmacometrics)1) the predictive capacity of two previously derived population pharmacokinetic models of tacrolimus in paediatric liver transplant recipients were tested during Bayesian forecasting 2) a new population pharmacokinetic model was developed focusing on the immediate post-transplant period and 3) this new model was applied in a simulation exercise to devise a new dosing scheme for initial oral dosing of tacrolimus. Pharmacokinetic, demographic and covariate data were collected retrospectively from patient records. The Abbottbase PKS program was used for Bayesian forecasting. Actual tacrolimus concentrations were compared to those predicted by the program and bias and precision determined. The NONMEM program was used for building of a new population pharmacokinetic model. Factors screened for influence on the pharmacokinetic parameters were weight, age, sex, post-operative day, whole/cut-down donor liver, haematocrit, serum albumin, bilirubin, serum creatinine, creatinine clearance, liver function tests and country of origin. Data were collected from 20 patients for Bayesian forecasting and from 73 patients for population pharmacokinetic modelling. Predictive performance of the two previous population models was poor in the immediate post-transplant period (range of precision, bias). Tacrolimus pharmacokinetics appeared to change rapidly over this period. During the first and third month after transplantation use of only one previous sample during Bayesian forecasting providing the best predictive performance. The final population model estimated a typical apparent clearance of tacrolimus of 0.
