Journal ArticleDOI
The pharmacokinetic‐pharmacodynamic relationship for mycophenolate mofetil in renal transplantation
M. D. Hale,Andrew J. Nicholls,Roy Bullingham,Ronald Hené,Andries J. Hoitsma,Jean-Paul Squifflet,Willem Weimar,Yves Vanrenterghem,Fokko J. Van de Woude,Gert A. Verpooten +9 more
TLDR
Mycophenolate mofetil, a pro‐drug for mycophenolic acid, reduces the likelihood of allograft rejection after renal transplantation and is studied in a randomized concentration‐controlled trial.Abstract:
Background: Mycophenolate mofetil, a pro-drug for mycophenolic acid, reduces the likelihood of allograft rejection after renal transplantation. We studied the relationship between mycophenolic acid pharmacokinetics and the likelihood of rejection in a randomized concentration-controlled trial. Methods: Under double-blind conditions, recipients of kidney transplants were followed for evidence of allograft rejection for 6 months. In addition to mycophenolate mofetil, patients received usual doses of cyclosporine (INN, ciclosporin) and corticosteroids, The dose of mycophenolate mofetil (given twice daily) was controlled by feedback, with mycophenolic acid area under the concentration-time curve (AUC) as the controlled variable. Patients were randomly assigned to 1 of 3 target AUC groups. Results: Logistic regression analysis showed a significant (P < .0001) relationship between mycophenolic acid AUC and the likelihood of rejection. High mycophenolic acid values were associated with a very low probability of rejection. An AUC of 15 mu g.h/mL yielded 50% of maximal achievable efficacy with a 4% change of efficacy for a 1 mu g.h/mL change in AUC at the midpoint of the logistic curve. Exploratory analyses showed other variables (eg, the maximum observed plasma concentration, predose plasma concentration, and drug dose) had poorer predictive power for the rejection outcome. Bivariate regression confirmed the importance of AUC as a highly predictive variable and showed low predictive value of other variables, once the contribution of AUC had been considered. The characteristic side effects of mycophenolate mofetil therapy appeared related to drug dose but not to mycophenolic acid concentration. Conclusions The AUC of mycophenolic acid is predictive of the likelihood of allograft rejection after renal transplantation in patients receiving mycophenolate mofetil.read more
Citations
More filters
Journal ArticleDOI
Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Solid Organ Transplant Recipients
TL;DR: This review aims to provide an extensive overview of the literature on the clinical pharmacokinetics of mycophenolate in solid organ transplantation and a briefer summary of current pharmacodynamic information.
Journal ArticleDOI
Recommendations for the Outpatient Surveillance of Renal Transplant Recipients
Bertram L. Kasiske,Bertram L. Kasiske,Miguel A. Vazquez,William E. Harmon,Robert S. Brown,Gabriel M. Danovitch,Robert S. Gaston,David M. Roth,John D. Scandling,Gary G. Singer +9 more
TL;DR: These guidelines are applicable to all adult and pediatric renal transplant recipients, and they cover the outpatient screening for and prevention of diseases and complications that commonly occur after renal transplantation.
Journal ArticleDOI
Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation.
Y. Le Meur,Mathias Büchler,Antoine Thierry,Sophie Caillard,Florence Villemain,Sylvie Lavaud,Isabelle Etienne,Pierre-François Westeel,B. H. de Ligny,Lionel Rostaing,Eric Thervet,Jean-Christophe Szelag,Jean-Philippe Rerolle,Alexandra Rousseau,Guy Touchard,Pierre Marquet +15 more
TL;DR: Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.
Journal ArticleDOI
Pharmacokinetic/Pharmacodynamic Modeling in Drug Development
Lewis B. Sheiner,J L Steimer +1 more
TL;DR: A framework for considering the role of pharmacokinetic/pharmacodynamic modeling in drug development and an appraisal of its current and potential impact on that activity is proposed and suggests that that work unit is the "in numero" study.
Journal ArticleDOI
Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid.
TL;DR: 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.
References
More filters
Journal ArticleDOI
Applied Logistic Regression.
TL;DR: Applied Logistic Regression, Third Edition provides an easily accessible introduction to the logistic regression model and highlights the power of this model by examining the relationship between a dichotomous outcome and a set of covariables.
Journal ArticleDOI
International standardization of criteria for the histologic diagnosis of renal allograft rejection : the Banff working classification of kidney transplant pathology
Kim Solez,Roy A. Axelsen,Hallgrimur Benediktsson,James F. Burdick,Arthur H. Cohen,Robert B. Colvin,Byron P. Croker,Dominique Droz,Michael S. Dunnill,Philip F. Halloran,Pekka Häyry,J. Charles Jennette,Paul Keown,Niels Marcussen,Michael J. Mihatsch,Kunio Morozumi,Bryan D. Myers,Cynthia C. Nast,Steen Olsen,Lorraine C. Racusen,E L Ramos,Seymour Rosen,David H. Sachs,Daniel R. Salomon,Fred Sanfilippo,Regina R. Verani,Eeva von Willebrand,Yutaka Yamaguchi +27 more
TL;DR: A schema for international standardization of nomenclature and criteria for the histologic diagnosis of renal allograft rejection was developed in Banff, Canada on August 2-4, 1991 and validated by the circulation of sets of slides for scoring by participant pathologists.
Journal ArticleDOI
Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group.
TL;DR: This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients.
Journal Article
Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection
Josep M. Grinyó,Carl-Gustav Groth,Rudolf Pichlmayr,Sa Sadek,Yves Vanrenterghem,M Behrend,R Luck,Francesc Moreso,J Peeters,J Rodicio,J Morales,Dagfinn Albrechtsen,P Fauchald,Sameh S. Sadek,J. P. A. Lodge,Jp Soulillou,Diego Cantarovich,van Willem Son,Adam Tegzess,Karl-Heinz Wagner,J Erhard,Christina Brattström,Lars Mjörnstedt,M. Wiesel,S. Carl,Hh Neumayer,Hauser,Peter Lang,B Bourgeon,Gunnar Tufveson,G. Gannedahl,Henrik Ekberg,N. Persson,A Tarantino,M Campise,G Thiel,M Zeiler,R Hene,G Ligtenberg,A Morgan,K Rigg,Hooftman L,K Hutchinson +42 more
TL;DR: MMF significantly reduced the rate of biopsy-proven rejection or other treatment failure during the first 6 months after transplantation and was well tolerated, although the 3 g dose was somewhat less well tolerated.
Journal ArticleDOI
A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation
Paul Keown,Pekka Häyry,Peter J. Morris,Calvin R. Stiller,Christopher M. Barker,Lisa Carr,David Landsberg,Ian R. Hardie,Russell J. Rigby,Helena Isoniemi,Derek W. R. Gray,Philip Belitsky,Allan McDonald,Tim Mathew,A. Clarkson,L. Barratt,B. Buchholz,Rowan Walker,Günther Kirste,Norman Muirhead,David J. Tiller,Geoff Duggin,Philip F. Halloran,Pierre Daloze,Gilles St. Louis,David Russell,David Ludwin,P. Vialtel,U. Binswanger,J. A C Buckels,Jean Louis Touraine,David P. Hickey,Giuseppe Remuzzi,Giuseppe Locatelli,F. T. Lam,Ed Tapper +35 more
TL;DR: MMF is associated with a significantly lower rate of treatment failure compared with AZA during the first 6 months after renal transplantation and produces a clinically important reduction in the incidence, severity, and treatment of acute graft rejection.
Related Papers (5)
Clinical Pharmacokinetics of Mycophenolate Mofetil
Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group.
Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection
Josep M. Grinyó,Carl-Gustav Groth,Rudolf Pichlmayr,Sa Sadek,Yves Vanrenterghem,M Behrend,R Luck,Francesc Moreso,J Peeters,J Rodicio,J Morales,Dagfinn Albrechtsen,P Fauchald,Sameh S. Sadek,J. P. A. Lodge,Jp Soulillou,Diego Cantarovich,van Willem Son,Adam Tegzess,Karl-Heinz Wagner,J Erhard,Christina Brattström,Lars Mjörnstedt,M. Wiesel,S. Carl,Hh Neumayer,Hauser,Peter Lang,B Bourgeon,Gunnar Tufveson,G. Gannedahl,Henrik Ekberg,N. Persson,A Tarantino,M Campise,G Thiel,M Zeiler,R Hene,G Ligtenberg,A Morgan,K Rigg,Hooftman L,K Hutchinson +42 more
A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation
Paul Keown,Pekka Häyry,Peter J. Morris,Calvin R. Stiller,Christopher M. Barker,Lisa Carr,David Landsberg,Ian R. Hardie,Russell J. Rigby,Helena Isoniemi,Derek W. R. Gray,Philip Belitsky,Allan McDonald,Tim Mathew,A. Clarkson,L. Barratt,B. Buchholz,Rowan Walker,Günther Kirste,Norman Muirhead,David J. Tiller,Geoff Duggin,Philip F. Halloran,Pierre Daloze,Gilles St. Louis,David Russell,David Ludwin,P. Vialtel,U. Binswanger,J. A C Buckels,Jean Louis Touraine,David P. Hickey,Giuseppe Remuzzi,Giuseppe Locatelli,F. T. Lam,Ed Tapper +35 more