BACKGROUND: We report a feasibility study based on our large-scale experience with mycophenolate mofetil dose adjustment based on mycophenolic acid interdose area under the curve (AUC) in renal transplant patients. METHODS: Between 2005 and 2010, 13,930 requests for 7090 different patients (outside any clinical trial) were posted by more than 30 different transplantation centers on a free, secure web site for mycophenolate mofetil dose recommendations using three plasma concentrations and Bayesian estimation. RESULTS: This retrospective study showed that 1) according to a consensually recommended 30- to 60-mg·h/L target, dose adjustment was needed for approximately 35% of the patients, 25% being underexposed with the highest proportion observed in the first weeks after transplantation; 2) when dose adjustment had been previously proposed, the subsequent AUC was significantly more often in the recommended range if the dose was applied than not at all posttransplantation periods (72-80% vs. 43-54%); and 3) the interindividual AUC variability in the "respected-dose" group was systematically lower than that in the "not respected-dose" group (depending on the posttransplantation periods; coefficient of variation %, 31-41% vs 49-70%, respectively). Further analysis suggested that mycophenolic acid AUC should best be monitored at least every 2 weeks during the first month, every 1 to 3 months between months 1 and 12, whereas in the stable phase, the odds to be still in the 30- to 60-mg·h/L range on the following visit was still 75% up to 1 year after the previous dose adjustment. CONCLUSION: This study showed that the monitoring of mycophenolate mofetil on the basis of AUC measurements is a clinically feasible approach, apparently acceptable by the patients, the nurses, and the physicians owing to its large use in routine clinics.
BACKGROUND: We report a feasibility study based on our large-scale experience with mycophenolate mofetil dose adjustment based on mycophenolic acid interdose area under the curve (AUC) in renal transplant patients. METHODS: Between 2005 and 2010, 13,930 requests for 7090 different patients (outside any clinical trial) were posted by more than 30 different transplantation centers on a free, secure web site for mycophenolate mofetil dose recommendations using three plasma concentrations and Bayesian estimation. RESULTS: This retrospective study showed that 1) according to a consensually recommended 30- to 60-mg·h/L target, dose adjustment was needed for approximately 35% of the patients, 25% being underexposed with the highest proportion observed in the first weeks after transplantation; 2) when dose adjustment had been previously proposed, the subsequent AUC was significantly more often in the recommended range if the dose was applied than not at all posttransplantation periods (72-80% vs. 43-54%); and 3) the interindividual AUC variability in the "respected-dose" group was systematically lower than that in the "not respected-dose" group (depending on the posttransplantation periods; coefficient of variation %, 31-41% vs 49-70%, respectively). Further analysis suggested that mycophenolic acid AUC should best be monitored at least every 2 weeks during the first month, every 1 to 3 months between months 1 and 12, whereas in the stable phase, the odds to be still in the 30- to 60-mg·h/L range on the following visit was still 75% up to 1 year after the previous dose adjustment. CONCLUSION: This study showed that the monitoring of mycophenolate mofetil on the basis of AUC measurements is a clinically feasible approach, apparently acceptable by the patients, the nurses, and the physicians owing to its large use in routine clinics.
Authors: Teun van Gelder; Yann Le Meur; Leslie M Shaw; Michael Oellerich; David DeNofrio; Curtis Holt; David W Holt; Bruce Kaplan; Dirk Kuypers; Bruno Meiser; Burkhard Toenshoff; Richard D Mamelok Journal: Ther Drug Monit Date: 2006-04 Impact factor: 3.681
Authors: Leslie M Shaw; Michal Figurski; Michael C Milone; Jennifer Trofe; Roy D Bloom Journal: Clin J Am Soc Nephrol Date: 2007-08-16 Impact factor: 8.237
Authors: Wolfgang Arns; Diane M Cibrik; Rowan G Walker; Georges Mourad; Klemens Budde; Edgar A Mueller; Flavio Vincenti Journal: Transplantation Date: 2006-10-27 Impact factor: 4.939
Authors: Y Le Meur; M Büchler; A Thierry; S Caillard; F Villemain; S Lavaud; I Etienne; P-F Westeel; B Hurault de Ligny; L Rostaing; E Thervet; J C Szelag; J-P Rérolle; A Rousseau; G Touchard; P Marquet Journal: Am J Transplant Date: 2007-10-01 Impact factor: 8.086
Authors: Gunnar Brandhorst; Pierre Marquet; Leslie M Shaw; Gerhard Liebisch; Gerd Schmitz; Mary Jane Coffing; Ingrid Domke; Frank Streit; Hilmar Luthe; Michael Oellerich Journal: Ther Drug Monit Date: 2008-08 Impact factor: 3.681
Authors: Brenda C M de Winter; Ron A A Mathôt; Reinier M van Hest; Teun van Gelder Journal: Expert Opin Drug Metab Toxicol Date: 2007-04 Impact factor: 4.481
Authors: E Comets; B Diquet; S Legrain; M-G Huisse; A Godon; C Bruhat; M-P Chauveheid; S Delpierre; X Duval; G Berrut; C Verstuyft; M-C Aumont; F Mentré Journal: Clin Pharmacol Ther Date: 2012-05 Impact factor: 6.875
Authors: Flora T Musuamba; Michel Mourad; Vincent Haufroid; Martine De Meyer; Arnaud Capron; Isabelle K Delattre; Roger K Verbeeck; Pierre Wallemacq Journal: Br J Clin Pharmacol Date: 2013-05 Impact factor: 4.335
Authors: David K Metz; Nick Holford; Joshua Y Kausman; Amanda Walker; Noel Cranswick; Christine E Staatz; Katherine A Barraclough; Francesco Ierino Journal: Transplantation Date: 2019-10 Impact factor: 4.939
Authors: Yewei Chen; Li Sun; Hong Xu; Min Dong; Tomoyuki Mizuno; Alexander A Vinks; Hermine I Brunner; Yifan Li; Zhiping Li Journal: Front Pharmacol Date: 2020-12-21 Impact factor: 5.810