WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Strategies that are more elaborate than measuring predose plasma concentrations are required for the therapeutic monitoring of mycophenolic acid (MPA). * Previous studies in healthy subjects and diabetes patients have suggested that MPA pharmacokinetics are influenced by gastric emptying, but this has not been demonstrated directly. WHAT THIS STUDY ADDS: * This study has investigated the relationship between gastric emptying, measured directly (using the (14)C octanoate and (13)C glycine breath tests) and the steady-state plasma concentration-time profile of MPA. * Delayed gastric emptying was associated with a longer t(max) and lower C(max), but total exposure to MPA was not affected. * The findings suggest that it could be misleading to rely fully on short-term (<2 h) limited sampling strategies for MPA therapeutic monitoring in recipients with gastric emptying disorders, the latter occurring relatively frequently in solid organ transplantation. AIM: To investigate the effect of gastric emptying on the pharmacokinetics of mycophenolic acid (MPA) in renal transplant patients. METHODS: We assessed the effect of gastric emptying on the disposition of MPA in 27 stable renal allograft recipients at 2 years after transplantation. Gastric emptying was measured by the (14)C-octanoate and (13)C-glycine breath test. RESULTS: Delayed gastric emptying was associated with a significantly longer MPA t(max)[1.0 (0.33-2.0) h vs. 0.5 (0.33-1.0) h; mean difference 0.39 h, 95% confidence interval (CI) 0.03, 0.75; P = 0.0289] and with a significant decrease in the maximum MPA concentration after dosing [10.6 (6.5-21.3) mg l(-1)vs. 20.1 (10.7-28.5) mg l(-1); mean difference 6.5 mg l(-1), 95% CI 2.1, 10.9; P = 0.0075]. Despite the substantial effect of delayed gastric emptying rates on MPA C(max) and t(max), total dose-interval exposure, measured by the MPA AUC(0-4), was not affected by the rate of gastric emptying [20.4 (13.9-43.0) mg h(-1) l(-1)vs. 22.4 (13.1-29.8) mg h(-1) l(-1)]. CONCLUSION: Delayed gastric emptying was associated with a slower absorption of MPA, a longer time to reach peak concentrations and lower maximum concentrations. These effects should be taken into account when validating limited (<2 h) sampling strategies to estimate total MPA exposure, which could be unreliable when monitoring patients with gastric emptying disorders.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Strategies that are more elaborate than measuring predose plasma concentrations are required for the therapeutic monitoring of mycophenolic acid (MPA). * Previous studies in healthy subjects and diabetespatients have suggested that MPA pharmacokinetics are influenced by gastric emptying, but this has not been demonstrated directly. WHAT THIS STUDY ADDS: * This study has investigated the relationship between gastric emptying, measured directly (using the (14)C octanoate and (13)C glycine breath tests) and the steady-state plasma concentration-time profile of MPA. * Delayed gastric emptying was associated with a longer t(max) and lower C(max), but total exposure to MPA was not affected. * The findings suggest that it could be misleading to rely fully on short-term (<2 h) limited sampling strategies for MPA therapeutic monitoring in recipients with gastric emptying disorders, the latter occurring relatively frequently in solid organ transplantation. AIM: To investigate the effect of gastric emptying on the pharmacokinetics of mycophenolic acid (MPA) in renal transplant patients. METHODS: We assessed the effect of gastric emptying on the disposition of MPA in 27 stable renal allograft recipients at 2 years after transplantation. Gastric emptying was measured by the (14)C-octanoate and (13)C-glycine breath test. RESULTS: Delayed gastric emptying was associated with a significantly longer MPA t(max)[1.0 (0.33-2.0) h vs. 0.5 (0.33-1.0) h; mean difference 0.39 h, 95% confidence interval (CI) 0.03, 0.75; P = 0.0289] and with a significant decrease in the maximum MPA concentration after dosing [10.6 (6.5-21.3) mg l(-1)vs. 20.1 (10.7-28.5) mg l(-1); mean difference 6.5 mg l(-1), 95% CI 2.1, 10.9; P = 0.0075]. Despite the substantial effect of delayed gastric emptying rates on MPA C(max) and t(max), total dose-interval exposure, measured by the MPA AUC(0-4), was not affected by the rate of gastric emptying [20.4 (13.9-43.0) mg h(-1) l(-1)vs. 22.4 (13.1-29.8) mg h(-1) l(-1)]. CONCLUSION: Delayed gastric emptying was associated with a slower absorption of MPA, a longer time to reach peak concentrations and lower maximum concentrations. These effects should be taken into account when validating limited (<2 h) sampling strategies to estimate total MPA exposure, which could be unreliable when monitoring patients with gastric emptying disorders.
Authors: Leslie M Shaw; Magdalena Korecka; Raman Venkataramanan; Lee Goldberg; Roy Bloom; Kenneth L Brayman Journal: Am J Transplant Date: 2003-05 Impact factor: 8.086
Authors: M Mourad; J Malaise; D Chaib Eddour; M De Meyer; J König; R Schepers; J P Squifflet; P Wallemacq Journal: Clin Chem Date: 2001 Impact factor: 8.327
Authors: M Morii; K Ueno; A Ogawa; R Kato; H Yoshimura; K Wada; H Hashimoto; M Takada; K Tanaka; T Nakatani; M Shibakawa Journal: Clin Pharmacol Ther Date: 2000-12 Impact factor: 6.875
Authors: Lutz T Weber; Maria Shipkova; Victor W Armstrong; Natalie Wagner; Ekkehard Schütz; Otto Mehls; Lothar B Zimmerhackl; Michael Oellerich; Burkhard Tönshoff Journal: J Am Soc Nephrol Date: 2002-03 Impact factor: 10.121
Authors: D R Kuypers; K Claes; P Evenepoel; B Maes; W Coosemans; J Pirenne; Y Vanrenterghem Journal: J Clin Pharmacol Date: 2003-08 Impact factor: 3.126
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