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Monitoring mycophenolic acid pharmacokinetic parameters in liver transplant recipients: Prediction of occurrence of leukopenia
Author(s) -
Hao Chen,
Anwei Mao,
Bing Chen,
Baiyong Shen,
Weixia Zhang,
Chuan Shen,
Erzhen Chen,
Xiaxing Deng,
Weihua Qiu,
Weiping Yang,
Chenghong Peng,
Hongwei Li
Publication year - 2008
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21600
Subject(s) - leukopenia , medicine , cmax , mycophenolic acid , pharmacokinetics , liver transplantation , tacrolimus , gastroenterology , area under the curve , transplantation , therapeutic drug monitoring , receiver operating characteristic , toxicity
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. Liver Transpl 14:1165–1173, 2008. © 2008 AASLD.