Therapeutic drug monitoring of mycophenolic acid can be used as predictor of clinical events for kidney transplant recipients treated with mycophenolate mofetil.
OBJECTIVE
This study was designed to investigate the relationship between clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplant patients.


METHODS
Thirty-seven adult kidney transplant recipients received a cyclosporine, mycophenolate mofetil, and steroids. MPA-AUC(0-12) was obtained before and 12 days after grafting by RP-HPLC. Predose blood samples were measured for MPA-C(0) were gathered from all the recipients at 4, 12, and 21 days as well as 1, 1.5, 2, 2.5, 3, and 6 months after grafting. The clinical events at corresponding time points were recorded to correlate with each MPA-C(0) value.


RESULTS
In addition to single-dose and multidose MPA-AUC(0-12), 357 MPA-C(0) values were obtained from 37 patients. The 357 units were divided into three subgroups: group A patients, including 239 units (66.9%), experienced uneventful outcomes; group B of 100 units (28.0%) showed MPA-related side effects, and group C, 18 units (5.0%) of acute rejection episodes. MPA-C(0) for groups A, B, and C were 0.8416 +/- 0.1373 mg/L, 1.5903 +/- 0.3741 mg/L and 0.6057 +/- 0.2338 mg/L, respectively (P < .001 between groups A and B, groups B and C, and P = .021 between groups A and C). The three groups were also divided into an initial phase (< or =1 month, 251 units) and a stable phase (>1 month, 106 units). The relationship between MPA-C(0) and associated clinical events was also investigated.


CONCLUSIONS
Our results suggested a relationship between MPA pharmacokinetics and clinical events. The MPA-C(0) might be an appropriate pharmacokinetic monitoring parameter for kidney transplantation.
Lu
Y P
YP
Transplantation Institute, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, China 610041. yipinglu@163.com
Zhu
Y C
YC
Liang
M Z
MZ
Nan
F
F
Yu
Q
Q
Wang
L
L
Wang
J
J
Li
Y P
YP
D000293:Adolescent; D000328:Adult; D002102:Cadaver; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D012372:ROC Curve; D014019:Tissue Donors
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid