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Title: Effects of gastric emptying on oral mycophenolic acid pharmacokinetics in stable renal allograft recipients
Authors: Naesens, Maarten ×
Verbeke, Kristin
Vanrenterghem, Yves
Kuypers, Dirk #
Issue Date: May-2007
Publisher: Blackwell Scientific Publications
Series Title: British journal of clinical pharmacology vol:63 issue:5 pages:541-547
Abstract: 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 associatedwith 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.
URI: 
ISSN: 0306-5251
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Nephrology
Translational Research in GastroIntestinal Disorders
Department of Microbiology & Immunology - miscellaneous
× corresponding author
# (joint) last author

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