Correlation of mycophenolic acid pharmacokinetic parameters with side effects in Chinese kidney transplant recipients treated with mycophenolate mofetil

2004 ◽  
Vol 36 (7) ◽  
pp. 2079-2081 ◽  
Author(s):  
Y.P. Lu ◽  
B. Lin ◽  
M.Z. Liang ◽  
L. Wang ◽  
F. Nan ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Side Effects ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Pharmacokinetic Parameters ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Evaluation of Limited Sampling Strategies for Mycophenolic Acid After Mycophenolate Mofetil Intake in Adult Kidney Transplant Recipients

2010 ◽  
Vol 32 (6) ◽  
pp. 723-733 ◽  
Author(s):  
Katherine A Barraclough ◽  
Nicole M Isbel ◽  
Michael E Franklin ◽  
Katie J Lee ◽  
Paul J Taylor ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Sampling Strategies ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Limited Sampling ◽  
Adult Kidney

Pharmacogenetics of Mycophenolate Mofetil in Patients Undergoing Hematopoietic Cell Transplantation (HCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3010-3010
Author(s):  
Janel Long ◽  
William S. Oetting ◽  
Wang Xinjing ◽  
Xianghua Luo ◽  
Marcie Tomblyn ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Plasma Concentrations ◽  
Hematopoietic Cell ◽  
Pharmacokinetic Parameters ◽  
Published Data ◽  
Kidney Transplant Recipients

Abstract Mycophenolate mofetil (MMF) is commonly used to provide host immunosuppression for hematopoietic cell engraftment and prevention of acute graft vs host disease (GVHD) in recipients of nonmyeloablative allogeneic HCT. There is wide variability in plasma concentrations of mycophenolic acid (MPA), the active metabolite of mycophenolate. Low MPA exposure is associated with poorer rates of engraftment and development of acute GVHD. This variability is not satisfactorily explained by hepatic or renal function suggesting variability may be due to genetic factors involved in drug metabolism or transport. MPA is glucuronidated by UDP glucuronosyltransferase enzymes UGT1A8, 1A9, and 1A10 to the primary metabolite, mycophenolic acid glucuronide (MPAG). MPAG is excreted into the urine and bile through multidrug resistant protein (MRP2) transporters. Several genetic variants of UGT enzymes and MRP2 are known to modify MPA pharmacokinetic parameters in kidney transplant recipients but have not been evaluated in HCT. We hypothesized that these variants are associated with systemic MPA and MPAG concentrations in HCT recipients. Recipient pretransplant DNA was obtained in 133 patients and evaluated for UGT1A8*2, UGT1A8*3, UGT1A9*2, UGT1A9*3, UGT1A9 T-275A, UGT1A9 C-2152T, UGT1A10*2, UGT2B7*2, MRP2 C-24T, MRP2 C-3972T, and MRP2 G-1249A. Patients received MMF at 1–1.5 gm IV or PO every 8–12 hours along with cyclosporine. Each subject had steady-state pharmacokinetics studied once or twice within the first 15 days of transplant for a total of 118 pharmacokinetic profiles. Frequencies of all variants were consistent with published data. Thirty three (24.8%) subjects were heterozygous (CT) and 3 (2.26%) were homozygous (TT) for the MRP2 C-24T variant. MRP2 C-3972T was heterozygous (CT) and homozygous (TT) in 56(42.2%) and 7(5.3%) individuals, respectively. In univariate analysis, there was no association between UGT variants and MPA IV or PO pharmacokinetics. Patients receiving oral MMF and carrying at least one MRP2 C-24T variant had significantly higher median (range) total dose adjusted MPAG Cmax 90.8ug/ml(40.0–164.8) vs 63.3(30.8–202.7), p= 0.02, trough 54.5ug/ml(16.1–99.6) vs 39.7(11.9–173.5), p=0.01 and MPAG Css 71.5ug/ml(28.9–123.0) vs 51.0(19.9–175.6), p=0.01. Similar results were observed for the C-3972T. These data suggest that single UGT variants do not significantly alter MPA exposure but MRP2 variants influence MPAG exposure. Reasons for observed UGT effects on MPA exposure in kidney transplant and not HCT remain unclear but may be due to bioavailability, lack of enterohepatic recycling due to gut decontamination, chemotherapy-induced mucosal and subclinical hepatic damage, and unidentified drug interactions. MRP2 variants may have an impact on other MRP2 substrates such as cyclophosphamide or inhibitors such as cyclosporine. A single UGT genotype to assist in dose selection is unlikely to be of clinical benefit; therefore the effect of combined variants should be explored.

Early Steroid Withdrawal and Optimization of Mycophenolic Acid Exposure in Kidney Transplant Recipients Receiving Mycophenolate Mofetil

2011 ◽  
Vol 92 (11) ◽  
pp. 1244-1251 ◽  
Author(s):  
Yannick Le Meur ◽  
Antoine Thierry ◽  
François Glowacki ◽  
Jean-Philippe Rerolle ◽  
Valerie Garrigue ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Acid Exposure ◽  
Steroid Withdrawal ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Association of ABCC2 Haplotypes to Mycophenolic Acid Pharmacokinetics in Stable Kidney Transplant Recipients

2021 ◽  
Author(s):  
Daniel Brazeau ◽  
Calvin J. Meaney ◽  
Joseph D. Consiglio ◽  
Gregory E. Wilding ◽  
Louise M. Cooper ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mycophenolic Acid Pharmacokinetics
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