Population pharmacokinetics of mycophenolic acid and dose optimization with limited sampling strategy in liver transplant children.

British Journal of Clinical Pharmacology
Caroline BarauAurélie Barrail-Tran

Abstract

The aims were to estimate the mycophenolic acid (MPA) population pharmacokinetic parameters in paediatric liver transplant recipients, to identify the factors affecting MPA pharmacokinetics and to develop a limited sampling strategy to estimate individual MPA AUC(0,12 h). Twenty-eight children, 1.1 to 18.0 years old, received oral mycophenolate mofetil (MMF) therapy combined with either tacrolimus (n= 23) or ciclosporin (n= 5). The population parameters were estimated from a model-building set of 16 intensive pharmacokinetic datasets obtained from 16 children. The data were analyzed by nonlinear mixed effect modelling, using a one compartment model with first order absorption and first order elimination and random effects on the absorption rate (k(a)), the apparent volume of distribution (V/F) and apparent clearance (CL/F). Two covariates, time since transplantation (≤ and >6 months) and age affected MPA pharmacokinetics. k(a), estimated at 1.7 h(-1) at age 8.7 years, exhibited large interindividual variability (308%). V/F, estimated at 64.7 l, increased about 2.3 times in children during the immediate post transplantation period. This increase was due to the increase in the unbound MPA fraction caused by the low albumin concen...Continue Reading

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Citations

Jul 19, 2013·Parasitology·Jeremy N BurrowsPaul Willis
May 6, 2014·Archives of Toxicology·Christine E Staatz, Susan E Tett
Aug 16, 2014·World Journal of Pediatrics : WJP·Wei ZhaoEvelyne Jacqz-Aigrain
Dec 20, 2013·Drug Metabolism and Pharmacokinetics·Min DongAlexander A Vinks
Nov 30, 2016·Therapeutic Drug Monitoring·Caroline BarauValérie Furlan
Mar 8, 2019·British Journal of Clinical Pharmacology·Reham AlmardiniJames C McElnay
Aug 26, 2014·World Journal of Gastroenterology : WJG·Hao Chen, Bing Chen
Oct 30, 2020·British Journal of Clinical Pharmacology·Yan RongTony K L Kiang

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