Literature DB >> 19339413

Pharmacodynamic evaluation of the first dose of mycophenolate mofetil before kidney transplantation.

Nassim Kamar1, Petra Glander, Jochen Nolting, Torsten Böhler, Pia Hambach, Lutz Liefeldt, Lionel Rostaing, Hans-Hellmut Neumayer, Klemens Budde.   

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.

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Year:  2009        PMID: 19339413      PMCID: PMC2676180          DOI: 10.2215/CJN.04860908

Source DB:  PubMed          Journal:  Clin J Am Soc Nephrol        ISSN: 1555-9041            Impact factor:   8.237


  29 in total

1.  Non-radioactive determination of inosine 5'-monophosphate dehydro-genase (IMPDH) in peripheral mononuclear cells.

Authors:  P Glander; K P Braun; P Hambach; S Bauer; I Mai; I Roots; J Waiser; L Fritsche; H H Neumayer; K Budde
Journal:  Clin Biochem       Date:  2001-10       Impact factor: 3.281

2.  Pharmacodynamic monitoring of mycophenolate mofetil in renal allograft recipients.

Authors:  K Budde; P Glander; K P Braun; T Böhler; J Waiser; L Fritsche; I Mai; H Neumayer
Journal:  Transplant Proc       Date:  2001 Nov-Dec       Impact factor: 1.066

Review 3.  Pharmacodynamics of immunosuppressive drugs.

Authors:  C Dambrin; J Klupp; R E Morris
Journal:  Curr Opin Immunol       Date:  2000-10       Impact factor: 7.486

Review 4.  How pharmacokinetic and pharmacodynamic drug monitoring can improve outcome in solid organ transplant recipients.

Authors:  Jochen Klupp; David W Holt; Teun van Gelder
Journal:  Transpl Immunol       Date:  2002-05       Impact factor: 1.708

5.  Pharmacodynamic monitoring of mycophenolate mofetil in stable renal allograft recipients.

Authors:  K Budde; K-P Braun; P Glander; T Böhler; P Hambach; L Fritsche; J Waiser; I Mai; H-H Neumayer
Journal:  Transplant Proc       Date:  2002-08       Impact factor: 1.066

6.  Flow cytometric quantitation of calcium-dependent and -independent mitogen-stimulation of T cell functions in whole blood: inhibition by immunosuppressive drugs in vitro.

Authors:  M J Barten; J F Gummert; T van Gelder; R Shorthouse; R E Morris
Journal:  J Immunol Methods       Date:  2001-07-01       Impact factor: 2.303

7.  Mycophenolic acid-induced GTP depletion also affects ATP and pyrimidine synthesis in mitogen-stimulated primary human T-lymphocytes.

Authors:  Y Qiu; L D Fairbanks; K Rückermann; C M Hawrlowicz; D F Richards; B Kirschbaum; H A Simmonds
Journal:  Transplantation       Date:  2000-03-15       Impact factor: 4.939

8.  Pharmacodynamics of mycophenolate mofetil after heart transplantation: new mechanisms of action and correlations with histologic severity of graft rejection.

Authors:  Markus J Barten; Teun van Gelder; Jan F Gummert; Katrin Boeke; Randi Shorthouse; Margaret E Billingham; Randall E Morris
Journal:  Am J Transplant       Date:  2002-09       Impact factor: 8.086

9.  Novel assays of multiple lymphocyte functions in whole blood measure: new mechanisms of action of mycophenolate mofetil in vivo.

Authors:  Markus J Barten; Teun van Gelder; Jan F Gummert; Randi Shorthouse; Randall E Morris
Journal:  Transpl Immunol       Date:  2002-06       Impact factor: 1.708

10.  Mycophenolic acid inhibits IL-2-dependent T cell proliferation, but not IL-2-dependent survival and sensitization to apoptosis.

Authors:  Laurence Quéméneur; Monique Flacher; Luc-Marie Gerland; Martine Ffrench; Jean-Pierre Revillard; Nathalie Bonnefoy-Berard
Journal:  J Immunol       Date:  2002-09-01       Impact factor: 5.422

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  4 in total

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

Authors:  Tsuyoshi Fukuda; Jens Goebel; Håvard Thøgersen; Denise Maseck; Shareen Cox; Barbara Logan; Joseph Sherbotie; Mouin Seikaly; Alexander A Vinks
Journal:  J Clin Pharmacol       Date:  2010-04-23       Impact factor: 3.126

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

Authors:  M Grobman; D M Boothe; H Rindt; B G Williamson; M L Katz; J R Coates; C R Reinero
Journal:  J Vet Pharmacol Ther       Date:  2017-06-25       Impact factor: 1.786

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

Authors:  Charles D Varnell; Tsuyoshi Fukuda; Cassie L Kirby; Lisa J Martin; Barry L Warshaw; Hiren P Patel; Deepa H Chand; Gina-Marie Barletta; Scott K Van Why; Rene G VanDeVoorde; Donald J Weaver; Amy Wilson; Priya S Verghese; Alexander A Vinks; Larry A Greenbaum; Jens Goebel; David K Hooper
Journal:  Pediatr Transplant       Date:  2017-09-04

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

Authors:  Miroslav Dostalek; Reginald Y Gohh; Fatemeh Akhlaghi
Journal:  Ther Drug Monit       Date:  2013-06       Impact factor: 3.681

  4 in total

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