Individualized population pharmacokinetic model with limited sampling for cyclosporine monitoring after liver transplantation in clinical practice

Abstract

Background: We recently developed and validated limited sampling models (LSMs) for cyclosporine monitoring after orthotopic liver transplantation based on individualized population pharmacokinetic models with Bayesian modelling. Aim: To evaluate LSM in practice, and to seek optimal balance between benefit and discomfort. Methods: In 30 stable patients, more than 6 months after orthotopic liver transplantation, previously switched from trough- to 2 h post-dose (C2)-monitoring, we switched to 3-monthly LSM 0,1,2,3 h-monitoring. During 18 months we evaluated dose, creatinine clearance, calculated area under the curve, intra-patient pharmacokinetic variability and ability to assess systemic exposure by several previously validated LSMs. Results: Within patients, there was variability of cyclosporine-area under the curve with the same dose (CV of 15%). Compared to C2-monitoring, there was no significant difference in dose (P = 0.237), creatinine clearance (P = 0.071) and number of rejections. Some models showed excellent correlation and precision with LSM 0,1,2,3 h comparing area under the curves (0,2 h: r2 = 0.88; 0,1,3 h: r2 = 0.91; 0,2,3 h: r2 = 0.92, all P < 0.001) with no difference in advised dose. Conclusions: 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. © 2007 The Authors.