Population Pharmacokinetics and Pharmacogenetics of Mycophenolic Acid Following Administration of Mycophenolate Mofetil in De Novo Pediatric Renal‐Transplant Patients

@article{Zhao2010PopulationPA,
  title={Population Pharmacokinetics and Pharmacogenetics of Mycophenolic Acid Following Administration of Mycophenolate Mofetil in De Novo Pediatric Renal‐Transplant Patients},
  author={Wei Zhao and May Fakhoury and Georges Desch{\^e}nes and Gw{\'e}naelle Roussey and Karine Brochard and Patrick Niaudet and Michel Tsimaratos and Jean Luc Andr{\'e} and Sylvie Cloarec and Pierre Cochat and Albert Bensman and Said Azougagh and {\'E}velyne M. Jacqz-Aigrain},
  journal={The Journal of Clinical Pharmacology},
  year={2010},
  volume={50}
}
The objective was to develop a population pharmacokinetic‐pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal‐transplant patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal‐transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8–A9, UGT2B7, and ABCC2. Population… 
View on Wiley
ncbi.nlm.nih.gov
57 Citations
Highly Influential Citations
6
Background Citations
20
Methods Citations
3
Results Citations
9

57 Citations

Population pharmacokinetics and pharmacogenetics of once daily prolonged-release formulation of tacrolimus in pediatric and adolescent kidney transplant recipients
TLDR
The population pharmacokinetic model of tacrolimusPR was developed and validated in pediatric and adolescent kidney transplant patients and body weight and CYP3A5 polymorphism were identified as significant factors influencing pharmacokinetics.
Population pharmacokinetics of mycophenolic acid in pediatric renal transplant patients using parametric and nonparametric approaches.
Population pharmacokinetic-pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period.
TLDR
An integrated population PK-PD model of MPA has been developed in paediatric renal transplant recipients and may be implemented in a Bayesian algorithm to allow a PK- PD guided therapeutic drug monitoring strategy.
Variability of mycophenolic acid elimination in the renal transplant recipients – population pharmacokinetic approach
TLDR
A population pharmacokinetic model for clearance of mycophenolic acid in adult renal transplant recipients showed that clearance of the MPA was significantly influenced by age, total daily dose of MPA, creatinine clearance, albumin level, status and gender of a donor, and the nifedipine and tacrolimus co-therapy.
Steady-state pharmacokinetics of mycophenolic acid in renal transplant patients: exploratory analysis of the effects of cyclosporine, recipients’ and donors’ ABCC2 gene variants, and their interactions
TLDR
Donors’ ABCC2 1249G>A polymorphism enhances the renal CsA effect, while recipients’ polymorphism seems to enhance the liver and the gutCsA effects.
UGT1A9, UGT2B7, and MRP2 Genotypes Can Predict Mycophenolic Acid Pharmacokinetic Variability in Pediatric Kidney Transplant Recipients
TLDR
It is demonstrated that combined UGT1A9-440C>T, UGT2B7-900A>G, and MRP2-24T>C polymorphisms can be important predictors of interindividual variability in MPA exposure in the pediatric population.
Population Pharmacokinetics and Pharmacogenetics of Everolimus in Renal Transplant Patients
TLDR
Maintaining everolimus systemic exposure at an AUC12 of 120 120 μg · h/L resulted in low rejection rates but considerable numbers of adverse events and toxicity, and a two-compartment pharmacokinetic model with lag-time describing the concentration-time profile of oralEverolimus in renal transplant patients has been developed using pharmacokinetics modelling.
Population pharmacokinetics of mycophenolic acid in paediatric patients
TLDR
This narrative review was to provide an up‐to‐date critique of currently available paediatric MPA population pharmacokinetic models, with emphases on modelling techniques, pharmacological findings and clinical relevance.
Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients with Autoimmune Disease
TLDR
MPA exposure correlated well with treatment efficacy in patients with autoimmune disease (response to treatment, active disease and disease markers); however, the relationship between MPA exposure and adverse events (infectious episodes, haematological toxicity and gastrointestinal symptoms) was unclear and further investigation is required.
4 Population pharmacokinetics and pharmacogenetics of everolimus in renal transplant patients
TLDR
A limited sampling strategy and pharmacokinetic model developed can be used to accurately estimate everolimus systemic exposure, an improvement compared to the widely used Ctrough monitoring.
...
...

References

SHOWING 1-10 OF 60 REFERENCES
Population Pharmacokinetics of Mycophenolic Acid in Kidney Transplant Pediatric and Adolescent Patients
TLDR
The results of this study combine the relationships between the pharmacokinetic parameters of MPA and patient covariates, which may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing pediatric patient care.
Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Recipients
TLDR
A population pharmacokinetic model for MPA following oral administration of mycophenolate mofetil is developed and identified correlations appear to explain part of the observed inter- and intrapatient pharmacokinetics variability.
Validation of an Abbreviated Pharmacokinetic Profile for the Estimation of Mycophenolic Acid Exposure in Pediatric Renal Transplant Recipients*
TLDR
Using an algorithm based on an abbreviated pharmacokinetic (PK) profile for the estimation of MPA exposure based on a limited sampling strategy during the first 2 hours after MMF dosing has the potential to optimize MMF therapy in pediatric renal transplant recipients.
Sirolimus Population Pharmacokinetic/Pharmacogenetic Analysis and Bayesian Modelling in Kidney Transplant Recipients
TLDR
An accurate population pharmacokinetic model showing the significant influence of the CYP3A5*1/*3 polymorphism on sirolimus apparent oral clearance is presented, and a Bayesian estimator accurately predicting siro Limus pharmacokinetics in patients co-administered mycophenolate mofetil, but no calcineurin inhibitor is developed.
AcylMPAG Plasma Concentrations and Mycophenolic Acid-Related Side Effects in Patients Undergoing Renal Transplantation Are Not Related to the UGT2B7-840G>A Gene Polymorphism
TLDR
No influence of the −840G>A UGT2B7 SNP on AcylMPAG exposure in patients undergoing renal transplantation is found and there also was no association between this variant genotype and the incidence of diarrhea or leucopenia, two adverse events for which a role for Ayl-glucuronide metabolite has been suggested.
Comparison of the Effects of Tacrolimus and Cyclosporine on the Pharmacokinetics of Mycophenolic Acid
TLDR
CsA inhibits MPAG excretion into bile and offer an explanation for the well-known increased MPA exposure in organ transplant patients caused by conversion from CsA-to TRL-based immunosuppression.
Population Pharmacokinetics and Bayesian Estimation of Mycophenolic Acid Concentrations in Stable Renal Transplant Patients
TLDR
For the first time, population pharmacokinetic data for MPA in stable renal transplant patients is reported, and it is shown that Bayesian estimation can allow accurate prediction of AUC with only three samples.
UGT Genotype May Contribute to Adverse Events Following Medication With Mycophenolate Mofetil in Pediatric Kidney Transplant Recipients
TLDR
The data implicate UGT polymorphisms associated with altered drug exposure as potential predictors of MMF adverse events.
Maximum A Posteriori Bayesian Estimation of Mycophenolic Acid Pharmacokinetics in Renal Transplant Recipients at Different Postgrafting Periods
TLDR
Maximum a posteriori probability (MAP) Bayesian estimators of mycophenolic acid (MPA) pharmacokinetics (PK) capable of accurately estimating the MPA interdose AUC in renal transplant patients using a limited number of blood samples are developed.
Time-dependent clearance of mycophenolic acid in renal transplant recipients.
TLDR
By monitoring creatinine clearance, albumin concentration, haemoglobin and cyclosporin predose concentration, changes in MPA exposure over time can be predicted and can be used to optimize therapy with mycophenolate mofetil.
...
...