Variability in free mycophenolic acid exposure in adult liver transplant recipients during the early posttransplantation period.
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 x h/L) was significantly lower than in groups B (45.2 mg x h/L, P = .031) and C (43.5 mg x h/L, P = .004). Free MPA AUC(0-12) was comparable whatever the time (0.41, 0.34, and 0.33 mg x 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.
Laboratoire de Pharmacologie-toxicologie, Service de Pharmacie, GH Cochin-Saint Vincent-de-Paul, 75014 Paris, France.
Anne Sophie
AS
Benichou
Benoit
B
Blanchet
Filomena
F
Conti
Maryline
M
Hornecker
Denis
D
Bernard
Fabrice
F
Taieb
Olivier
O
Scatton
Halim
H
Abbas
Laura
L
Harcouet
Alain
A
Dauphin
Yvon
Y
Calmus
Michel
M
Tod
D019540:Area Under Curve; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid