Pharmacodynamic Evaluation of the First Dose of Mycophenolate Mofetil Before Kidney Transplantation

Overview

Journal Clin J Am Soc Nephrol

Specialty Nephrology

Date 2009 Apr 3

PMID 19339413

Citations 4

Authors

Nassim Kamar

Petra Glander

Jochen Nolting

Torsten Bohler

Pia Hambach

Lutz Liefeldt

Lionel Rostaing

Hans-Hellmut Neumayer

Klemens Budde

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: The effect of mycophenolate mofetil (MMF) on T cell function has not been evaluated in patients undergoing kidney transplantation. The aim of this study was to assess the effect of 1g of MMF on T cell function, that is, intralymphocyte cytokine expression, T cell activation (CD25 and CD71), and T cell proliferation, as well as inosine monophosphate dehydrogenase (IMPDH) activity, to better understand the relationship between pharmacokinetic and pharmacodynamic markers in patients receiving the first dose of MMF before kidney transplantation.

Patients: Twenty-four patients undergoing a kidney transplantation from a living donor were enrolled in this study.

Results: Compared with baseline (before MMF intake), T cell proliferation (93%), IMPDH activity (74%), CD25 (46%), and CD71 (50%) expression significantly decreased during the first hour after MMF intake, in parallel to the rise in MPA concentration. Thereafter, all pharmacodynamic markers, except IMPDH activity, returned back to baseline level. There was a complex inverse relationship between pharmacokinetic and pharmacodynamic markers. The inhibition of T cell proliferation was highly correlated to IMPDH activity, but also to T cell activation markers.

Conclusion: The administration of MMF to patients is associated not only with a dramatic decrease in both T cell proliferation and IMPDH activity, but also with in a decrease in CD25 and CD71 expression.

Citing Articles

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs.

Varnell C, Fukuda T, Kirby C, Martin L, Warshaw B, Patel H Pediatr Transplant. 2017; 21(7).

PMID: 28869324 PMC: 5905326. DOI: 10.1111/petr.13033.

Pharmacokinetics and dynamics of mycophenolate mofetil after single-dose oral administration in juvenile dachshunds.

Grobman M, Boothe D, Rindt H, Williamson B, Katz M, Coates J J Vet Pharmacol Ther. 2017; 40(6):e1-e10.

PMID: 28649788 PMC: 5673552. DOI: 10.1111/jvp.12420.

Inosine monophosphate dehydrogenase expression and activity are significantly lower in kidney transplant recipients with diabetes mellitus.

Dostalek M, Gohh R, Akhlaghi F Ther Drug Monit. 2013; 35(3):374-83.

PMID: 23666569 PMC: 4109137. DOI: 10.1097/FTD.0b013e3182852697.

Inosine monophosphate dehydrogenase (IMPDH) activity as a pharmacodynamic biomarker of mycophenolic acid effects in pediatric kidney transplant recipients.

Fukuda T, Goebel J, Thogersen H, Maseck D, Cox S, Logan B J Clin Pharmacol. 2010; 51(3):309-20.

PMID: 20418509 PMC: 3769694. DOI: 10.1177/0091270010368542.

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