不同剂型吗替麦考酚酯对肾移植后早期受者药物代谢动力学和疗效比较

目的比较吗替麦考酚酯分散片（商品名顺友）与片剂（商品名骁悉）在肾移植术后早期麦考酚酸（mycophenolicacid，MPA）浓度随时间的变化及疗效。方法30例首次肾移植受者随机分为顺友组和骁悉组，于术后24h内开始口服顺友或骁悉，均为1．5g／d，一日两次。术后第7、14天分别于服药前（0h）及服药后0．5、1、1．5、2、3、4、6、8、10、12h采集外周静脉血，用高效液相色谱分析法测定MPA血药浓度，比较两组MPA的达峰时间（MPA—Tmax）、峰浓度（MPA—Cmax）及浓度一时间曲线下面积（MPA—AUC0.12h），同时比较两组术后早期移植肾功能及3个月内的急性排斥反应和不良反应发生率。结果顺友组和骁悉组MPA—Tmax第7天[（1．27±0．88）h比（1．27±0．68）h，P〉0．05）]、第14天[（0．73±0．32）h比（0．80±0．46）h，P〉0．05）差异均无统计学意义，两组第14天MPA—Tmax均比各组内第7天提前（均P〈0．05）。两组MPA—Cmax第7天[（12．104-5．00）ng/mL比（12．20±5．60）ng／mL，P〉0．05）、第14天[（15．40±6．36）ng／mL比（12．80±6．36）ng／mL，P〉0．05）无差异，组内比较均无差异（P〉0．05）。两组MPA—AUC0_12h第7天[（31．90±15．62）mg·h·L^-1比（31．50±12．88）mg·h·L^-1，P〉0．05）、第14天[（33．30±8．68）mg·h·L^-1比（34．30±7．31）mg·h·L^-1，P〉0．05]差异无统计学意义，第14天均高于各组内第7天值，但差异无统计学意义（P〉0．05）。两组术后早期血肌酐浓度差异无统计学意义。顺友组和骁悉组均无急性排斥反应发生，两组分别有4例、3例受者发生不良反应。结论顺友和骁悉在肾移植受者术后早期MPA血药浓度变化和疗效无明显差异。顺友用于肾移植后早期的联合免疫抑制治疗安全有效，其远期效果有待进一步研究。

The pharmacokinetic features and therapeutic effects of two formulations of mycophenolate mofetil in renal transplant recipients at the early postoperative stage

Objective To compare the basic pharmacokinetic features of mycophenolic acid （MPA） in renal transplant recipients at the early postoperative stage when mycophenolate mofetil dispersible tablets （MMF-DT） or mycophenloate mofetil tablets （MMF-T） were administered, and to observe both therapeutic effects. Methods Thirty de novo renal transplant recipients were randomly divided into the MMF-DT group and MMF-T group. Both drugs were administered twice daily, 1.5 g per day, initiating within 24 h posttransplantation. Peripheral vein blood samples were harvested at right before drug administration and 0.5, 1, 1.5, 2, 3,4, 6, 8, 10, 12 h after administration on day 7 and 14 posttransplant. The MPA concentration was monitored by high performance liquid chromatography. Maximum concentration （ MPA-Cmax ）, time to Cmax （ MPA-Tmax ）, and area under curve （ MPA- AUC0.12 h） were compared, as well as renal graft function, acute rejection, and side effect rates.Results In the MMF-DT and MMF-T groups, MPA-Tmax were （ 1.27 ±0.88） and （ 1.27 ±0.68） h on day7 （P〉0.05）, and （0.73±0.32） and （0.80±0.46） honday 14 （P〉0.05）. MPA-Tmax was shorter on day 14 than that on day 7 in both groups （P 〈 0.05 ）. MPA-Cmax were （12.10 ±5.00） and （12.20±5.60） ng/mL on day 7, and （15.40±6.36） and （12.80±6.36） ng/mL on day 14, with no in-group statistical difference in both groups （ P 〉 0.05）. MPA-AUC0-12 h were （31. 90 ± 15.62） and （31.50±12.88） mg·h·L^-1 on day 7, （33.30 ±8.68） and （34.30 ±7.31） mg·h·L^-1 on day 14. MPA-AUC0.12h increased on day 14, but no statistical difference was found （P 〉 0.05 ）. No significant difference was noted as compared serum creatinine levels in both groups. No acute rejection happened in both groups. Four patients in the MMF-DT group and 3 in the MMF-T group had side effects. Conclusions The basic pharmacokinetic features of MMF-DT and MMF-T and their therapeutic effects are not significantly different at