title: Monitoring mycophenolic acid pharmacokinetic parameters in liver transplant recipients: prediction of occurrence of leukopenia.
abstract: 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.
authors.affiliation: Center of Organ Transplantation, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. haochendr@yahoo.com.cn
authors.forename: Chen
authors.initials: C
authors.lastname: Hao
authors.forename: Mao
authors.initials: M
authors.lastname: Anwei
authors.forename: Chen
authors.initials: C
authors.lastname: Bing
authors.forename: Shen
authors.initials: S
authors.lastname: Baiyong
authors.forename: Zhang
authors.initials: Z
authors.lastname: Weixia
authors.forename: Shen
authors.initials: S
authors.lastname: Chuan
authors.forename: Chen
authors.initials: C
authors.lastname: Erzhen
authors.forename: Deng
authors.initials: D
authors.lastname: Xiaxing
authors.forename: Qiu
authors.initials: Q
authors.lastname: Weihua
authors.forename: Yang
authors.initials: Y
authors.lastname: Weiping
authors.forename: Peng
authors.initials: P
authors.lastname: Chenghong
authors.forename: Li
authors.initials: L
authors.lastname: Hongwei
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid