Pharmacokinetics of mycophenolic acid in living donor liver transplantation.
OBJECTIVE
This study sought to define the pharmacokinetics of mycophenolic acid (MPA) in Korean living donor liver transplant recipients.


METHODS
Thirty-two liver transplant recipients (29 males, 3 females) were administered 750 mg mycophenolate mofetil (MMF) twice daily with concomitant tacrolimus. Plasma MPA concentrations were measured by liquid chromatography with tandem mass spectrometry detection assay from samples drawn before dosing (C0) and after dosing at 0.5 hours (C1/2) and 2 hours (C2), providing a total of 114 pharmacokinetic profiles at various periods from 3 days to 6 months posttransplantation (D3, D7, D14, M1, M3, and M6).


RESULTS
The mean area-under-the-curve from 0 to 2 hours (AUC0-2) was 30.0+/-11.6 microg.h/mL (range, 7.8-60.7). Of 114 pharmacokinetic profiles, 40 (35%) AUC and 7 (6.1%) trough values were within the target value (30-60 microg.h/mL and 1.7-4.0 microg/mL, respectively). The C0, C1/2, and C2 concentrations showed large interindividual variability: C0 (0.01-4.46 microg/mL), C1/2 (0.14-36.86 microg/mL), and C2 (0.79-18.19 microg/mL). A positive correlation was observed between AUC and C0 (r=.6374; P<.0001), and C2 (r=.7460; P<.0001). When analyzed according to the date posttransplant, a positive correlation between AUC and C0 was shown on day 7, day 14, and at month 1. There was no difference in any pharmacokinetic parameter relative to age, weight, or albumin level.


CONCLUSIONS
This study demonstrated that C0 values on day 7, day 14, and at month 1 provided valuable information for MPA monitoring. C0 was shown to be the most reliable monitoring time in relation to AUC. However, results from a larger randomized trial with more time intervals are eagerly awaited.
Shin
M
M
Division of Transplantation, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Moon
J I
JI
Kim
J M
JM
Choi
G-S
GS
Kwon
C H
CH
Kim
S-J
SJ
Joh
J-W
JW
Lee
S-K
SK
Lee
S-T
ST
Jung
H
H
Lee
S-Y
SY
D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007958:Leukocyte Count; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D019520:Living Donors; D008297:Male; D008775:Methylprednisolone / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D008775:Methylprednisolone