Monitoring mycophenolic acid pharmacokinetic parameters in liver transplant recipients: prediction of occurrence of leukopenia.
Mycophenolate mofetil (MMF) is a very powerful immunosuppressive drug used in preventing acute rejection in liver transplantation. However, MMF has some serious side effects, including hematologic and gastrointestinal disorders. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in Chinese liver transplant recipients. Sixty-three adult liver transplant recipients receiving 1.0 g of MMF twice daily in combination with tacrolimus were prospectively included. The MPA pharmacokinetic profiles (blood sampling time points: before the dose and 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after the dose) were monitored after transplantation. Every clinical event, including acute and MMF-related side effects, was monitored in all patients within 3 months. Two patients (3.2%) had an episode of acute rejection. Forty-two patients (66.7%) had 52 episodes of MMF-related side effects, including leukopenia, diarrhea, and infection. The 0-hour concentration (C(0h)), maximum (peak) concentration (C(max)), and area under the curve from 0 to 12 hours (AUC(0-12h)) in patients with side effects were significantly higher than those in patients without side effects (P < 0.05). The thresholds of side effects from receiver operating characteristic analysis were 2 mg/L (sensitivity, 52.4%; specificity, 90.5%) for C(0h), 10 mg/L (sensitivity, 45.2%; specificity, 85.7%) for C(max), and 40 mg h/L (sensitivity, 71.4%; specificity, 61.9%) for AUC(0-12h) (P < 0.05). Leukopenia was discriminated effectively in C(0h) and in C(max) (P < 0.05). These results demonstrate the close relationship between leukopenia and MPA pharmacokinetic parameters in the early period after liver transplantation. C(0h) and AUC(0-12h) of MPA could predict the subsequent occurrence of leukopenia. These values may be used in routine monitoring for MMF therapy.
Hao
Chen
C
Center of Organ Transplantation, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. haochendr@yahoo.com.cn
Anwei
Mao
M
Bing
Chen
C
Baiyong
Shen
S
Weixia
Zhang
Z
Chuan
Shen
S
Erzhen
Chen
C
Xiaxing
Deng
D
Weihua
Qiu
Q
Weiping
Yang
Y
Chenghong
Peng
P
Hongwei
Li
L
D000328:Adult; D000368:Aged; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D007239:Infections / Q000139:chemically induced; D007970:Leukopenia / Q000139:chemically induced*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D012372:ROC Curve
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid