SUMMARYBackground: New methods to estimate the systemic exposure to ciclosporin such as the level 2 h after dosing and limited sampling formulas may lead to improved clinical outcome after orthotopic liver transplantation. However, most strategies are characterized by rigid sampling times. Aim: To develop and validate a flexible individualized population-pharmacokinetic model for ciclosporin monitoring in orthotopic liver transplantation. Methods: A total of 62 curves obtained from 31 patients at least 0.5 year after orthotopic liver transplantation were divided into two equal groups. From 31 curves, relatively simple limited sampling formulas were derived using multiple regression analysis, while using pharmacokinetic software a two-compartment populationpharmacokinetic model was derived from these same data. We then tested the ability to estimate the AUC by the limited sampling formulas and a different approach using several limited sampling strategies on the other 31 curves. The new approach consists of individualizing the mean a priori population-pharmacokinetic parameters of the two-compartment population-pharmacokinetic model by means of maximum a posteriori Bayesian fitting with individual data leading to an individualized population-pharmacokinetic limited sampling model. From the individualized pharmacokinetic parameters, AUC 0-12h was calculated for each combination of

The limited sampling model, with only trough- and 2-h sampling, yields excellent accuracy and assesses systemic exposure much better than C2 with less bias and greater precision. Considering the calculated intra-patient variability, more precision is redundant, so LSM 0,2 h seems the optimal way of cyclosporine-monitoring.

No abstract