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Variability in Free Mycophenolic Acid Exposure in Adult Liver Transplant Recipients During the Early Posttransplantation Period
Author(s) -
Benichou Anne Sophie,
Blanchet Benoit,
Conti Filomena,
Hornecker Maryline,
Bernard Denis,
Taieb Fabrice,
Scatton Olivier,
Abbas Halim,
Harcouet Laura,
Dauphin Alain,
Calmus Yvon,
Tod Michel
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009358084
Subject(s) - mycophenolate , mycophenolic acid , free fraction , pharmacokinetics , dosing , liver transplantation , medicine , population , transplantation , urology , area under the curve , chemistry , pharmacology , gastroenterology , environmental health
Mycophenolate mofetil (MMF) pharmacokinetics variability in liver transplant recipients during the early posttransplantation period may be related to changes in mycophenolic acid (MPA) protein binding. This study aimed at characterizing the variation of free MPA exposure with respect to time since transplantation. Three groups (A, B, C) were compared. The median posttransplantation time was 12 days (A, n = 26 pharmacokinetic sessions), 36 days (B, n = 25), and 867 days (C, n = 21). The median MPA AUC 0–12 in group A (26.8 mg·h/L) was significantly lower than in groups B (45.2 mg·h/L, P = .031) and C (43.5 mg·h/L, P = .004). Free MPA AUC 0–12 was comparable whatever the time (0.41, 0.34, and 0.33 mg·h/L, respectively). MPA apparent clearance (CL/F) was significantly correlated with MPA free fraction (r = 0.60, P < .0001) and approximately 1.7‐fold higher in group A compared to groups B and C (P < .05). Enhanced CL/F in relation with an increase in MPA free fraction results in a low AUC of total MPA during the first postoperative month, but on average, at the population level, the exposure to free MPA is not altered, suggesting that total MPA AUC should not be used to adapt MMF dosing during this period.