Population pharmacokinetics of mycophenolic acid in children and young people undergoing blood or marrow and solid organ transplantation.
Br J Clin Pharmacol
; 70(4): 567-79, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20840448
ABSTRACT
AIMS:
To characterize the population pharmacokinetics of mycophenolic acid (MPA) and evaluate dose regimens using a simulation approach and accepted therapeutic drug monitoring targets in children and young people undergoing blood or marrow, kidney and liver transplantation.METHODS:
MPA concentration-time data were collected using an age specific sampling protocol over 12h. Some patients provided randomly timed but accurately recorded blood samples. Total and unbound MPA were measured by HPLC. NONMEM was employed to analyze MPA pharmacokinetic data. Simulations (n= 1000) were conducted to assess the suitability of the MPA dose regimens to maintain total MPA AUC(0,12h) within the range 30 and 60mg l(-1) h associated with optimal outcome.RESULTS:
A two-compartment pharmacokinetic model with first-order elimination best described MPA concentration-time data. Population mean estimates of MPA clearance, inter-compartmental clearance, volumes of distribution in the central and peripheral compartments, absorption rate constant and bioavailability were 6.42 l h(-1) , 3.74 l h(-1) , 7.24 l, 16.8l, 0.39h(-1) and 0.48, respectively. Inclusion of bodyweight and concomitant ciclosporin reduced the inter-individual variability in CL from 54.3% to 31.6%. Children with a bodyweight of 10kg receiving standard MPA dose regimens achieve an MPA AUC below the target range suggesting they may be at a greater risk of acute rejection.CONCLUSIONS:
The population pharmacokinetic model for MPA can be used to explore dosing guidelines for safe and effective immunotherapy in children and young people undergoing transplantation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transfusión Sanguínea
/
Trasplante de Órganos
/
Trasplante de Médula Ósea
/
Inmunosupresores
/
Ácido Micofenólico
Tipo de estudio:
Guideline
Límite:
Adolescent
/
Adult
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2010
Tipo del documento:
Article