AIMS: To develop a limited sampling strategy to determine ciclosporin systemic exposure [area-under-the-curve(AUC)]. This is meant to be the first step in a future study of the relationship between AUC and the biological effects of ciclosporin. METHODS: The pharmacokinetics of ciclosporin was investigated prospectively following stem cell transplantation (SCT) in 17 children, aged 1.8-16.1 years. Ciclosporin was given twice daily, intravenously over a short infusion of 2 h duration during the early post-SCT period, or orally later on, when oral medication was well tolerated. Parameter estimation was performed using nonlinear mixed effect modelling as implemented in the NONMEM program. Individual empirical Bayes estimates of clearance and distribution volume were correlated with the demographic variables. RESULTS: Pharmacokinetics was described adequately with a two-compartment model with lag time (population estimates: CL = 11.3 l h(-1); V(c) = 16.5 l; V(p) = 59.9 l; t(1/2) absorption = 0.78 h, t(lag) = 0.6 h). The AUCs, determined for the combination of trough level with one time point between 2 and 3 h after dosing, correlated very well with the reference AUC (r(2) = 0.97). No correlation was found between clearance and distribution volume, and the demographic patient variables length, body weight, age and glomerular filtration rate. CONCLUSION: A two-point limited sampling strategy, in combination with a Bayesian fitting procedure using the pharmacokinetic population model described, can adequately determine the AUC of ciclosporin. Since no correlation between clearance and body weight was found, dosing ciclosporin per kg bodyweight is not supported by the results of this study. We suggest starting with a fixed dose, followed by AUC determination and dose adjustment.
AIMS: To develop a limited sampling strategy to determine ciclosporin systemic exposure [area-under-the-curve(AUC)]. This is meant to be the first step in a future study of the relationship between AUC and the biological effects of ciclosporin. METHODS: The pharmacokinetics of ciclosporin was investigated prospectively following stem cell transplantation (SCT) in 17 children, aged 1.8-16.1 years. Ciclosporin was given twice daily, intravenously over a short infusion of 2 h duration during the early post-SCT period, or orally later on, when oral medication was well tolerated. Parameter estimation was performed using nonlinear mixed effect modelling as implemented in the NONMEM program. Individual empirical Bayes estimates of clearance and distribution volume were correlated with the demographic variables. RESULTS: Pharmacokinetics was described adequately with a two-compartment model with lag time (population estimates: CL = 11.3 l h(-1); V(c) = 16.5 l; V(p) = 59.9 l; t(1/2) absorption = 0.78 h, t(lag) = 0.6 h). The AUCs, determined for the combination of trough level with one time point between 2 and 3 h after dosing, correlated very well with the reference AUC (r(2) = 0.97). No correlation was found between clearance and distribution volume, and the demographic patient variables length, body weight, age and glomerular filtration rate. CONCLUSION: A two-point limited sampling strategy, in combination with a Bayesian fitting procedure using the pharmacokinetic population model described, can adequately determine the AUC of ciclosporin. Since no correlation between clearance and body weight was found, dosing ciclosporin per kg bodyweight is not supported by the results of this study. We suggest starting with a fixed dose, followed by AUC determination and dose adjustment.
Authors: Eduard M Scholten; Ajda T Rowshani; Serge Cremers; Frederike J Bemelman; Michael Eikmans; Erik van Kan; Marko J Mallat; Sandrine Florquin; Janto Surachno; Ineke J ten Berge; Ingeborg M Bajema; Johan W de Fijter Journal: J Am Soc Nephrol Date: 2006-08-09 Impact factor: 10.121
Authors: F Locatelli; M Zecca; R Rondelli; F Bonetti; G Dini; A Prete; C Messina; C Uderzo; M Ripaldi; F Porta; G Giorgiani; E Giraldi; A Pession Journal: Blood Date: 2000-03-01 Impact factor: 22.113
Authors: K R Schultz; T J Nevill; R F Balshaw; C L Toze; T Corr; C J Currie; D K Strong; P A Keown Journal: Bone Marrow Transplant Date: 2000-09 Impact factor: 5.483
Authors: P Bader; T Klingebiel; A Schaudt; U Theurer-Mainka; R Handgretinger; P Lang; D Niethammer; J F Beck Journal: Leukemia Date: 1999-12 Impact factor: 11.528
Authors: Kwi Suk Kim; Aree Moon; Hyoung Jin Kang; Hee Young Shin; Young Hee Choi; Hyang Sook Kim; Sang Geon Kim Journal: World J Transplant Date: 2016-06-24
Authors: Charlotte I S Barker; Eva Germovsek; Rollo L Hoare; Jodi M Lestner; Joanna Lewis; Joseph F Standing Journal: Adv Drug Deliv Rev Date: 2014-01-17 Impact factor: 15.470