Population pharmacokinetics of mycophenolic acid in senile Chinese kidney transplant recipients.
To explore the pharmacokinetic characteristics of mycophenolic acid (MPA) among elderly Chinese kidney transplant recipients, we enrolled 24 patients over 60 years old (65.6 +/- 3.6) as the (Gs) group and 24 patients of 39.6 +/- 14.3 years old as a control group (Ga). Venous blood samples were taken at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours after the morning dose of mycophenolate mofetil at 10 to 12 weeks posttransplant. Plasma MPA concentrations were measured by a validated high-performance liquid chromatography method. Within 6-month posttransplant follow-up, there had not been an acute rejection episode when five elderly and one other adult experienced severe adverse events (SAEs), such as pneumonia and leukocytopenia. MPA area under the curve (AUC) in Gs was significantly lower than that among Ga (P < .05), while there was no significant difference in predose, peak concentrations, or peak times (P > .05). The concentration-time curve of Gs showed a bipeak pattern in five patients (20.8%) during the early stage (2 to 4 hours postdose). AUC in the subgroup of Gs with SAEs (n = 5) was significantly higher than that of elderly subjects without SAEs (n = 19) (P = .042). When Gs were subdivided at a cutting AUC point of 25 mug/mL, the SAE incidence was significantly higher in the subgroup with a higher AUC than than those with the lower AUC (P = .047). Through multiple stepwise regression, we obtained a minimal model to estimate MPA AUC of elderly recipients: AUC = 3.0410 + 9.8588 x C(0) + 0.5963 x C(0.5) + 2.5612 x C(3) (R(2) = .893).
Wang
C X
CX
Organ Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. wcx6363@163.com
Meng
F H
FH
Chen
L Z
LZ
Ren
B
B
Li
S X
SX
Fei
J G
JG
Qiu
J
J
Deng
S X
SX
Li
J
J
Chen
S Y
SY
D000328:Adult; D000368:Aged; D000375:Aging; D019540:Area Under Curve; D002681:China; D016572:Cyclosporine / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D008111:Liver Function Tests; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid