联苯双酯对肾移植患者环孢素血药浓度的影响

Effect of bifendate on blood concentration of ciclosporin in renal transplantation patients

目的观察肾移植术后环孢素(CsA)与联苯双酯滴丸(BFD)合用时对CsA血药浓度的影响。方法肾移植术后(30±15)d,肝损伤患者40例,常规使用CsA+麦考酚吗乙酯(MMF)+泼尼松(Pred)抗排斥。当患者出现肝功能受损时开始服用BFD,首剂量为45 mg·d^(-1)。待肝功能正常后,BFD进行梯度减药(由45 mg·d^(-1)减至4.5 mg·d^(-1)),减药间隔时间为15 d。BFD用药期间,CsA用量(6.5±1.0)mg·kg^(-1)·d^(-1)不变。肾移植患者在保肝治疗前,每次更改BFD用药方案前及停BFD 15 d后测定CsA血药浓度,并行尿常规及肝、肾功能检测。结果40例肾移植患者保肝治疗前CsA血药浓度为(312.6±13)μg·L^(-1),服BFD首次剂量15 d后,CsA血药浓度降至(158.3±14)μg·L^(-1);经1～4次递减BFD后,CsA血药浓度分别为(161.2±13)、(188.1±16)、(204.1±15)、(221.7±11)μg·L^(-1);停服BFD 15 d后CsA血药浓度为(258.4±13)μg·L^(-1)。总胆红素(TB)由(30±5.0)μmol·L^(-1)降至(17±3.0)μmol·L^(-1),丙氨酸氨基转移酶(ALT)由(100±50)U·L^(-1)降至(30±10)U·L^(-1),尿量、尿常规、肾功能无明显变化。结论CsA与BFD合用,可导致CsA血药浓度下降。临床用药需注意监测,及时调整用药剂量,避免浓度过低,导致严重的移植肾排斥。

AIM To study the change of blood concentration of ciclosporin （CsA） in renal transplantation patients treated with the combination of bifendate （BFD） ＋CsA. METHODS Forty patients who got kidney transplantation after （30 ± 15） d with liver injury were treated routinely with the combination of CsA ＋ MMF ＋ prednisone. The blood concentration of CsA was determined by AXSYM （United States Abbott） plasma concentration detector before the patients took the medicine 30 min. CsA blood concentration, the amount of urine dose, liver function and renal function were determined before taking the medicine. BFD was reduced gradually by the interval of 15 d after patients got normal liver function. BFD remained at the dosage level of CsA （6.5 ± 1.0） mg·kg^-1·d^-1. In 15 d, the change of blood concentration of CsA was observed and recorded, avoiding other drugs which could interfere with blood concentration of CsA. At the same time, the relevant tests including the amount of urine dose, the urine routine test, the function of liver and kidney were reviewed. RESULTS In the treatment of 40 cases with BFD in 15 d, the blood concentration of CsA was （158.3 ± 14） μg·L^-1. After reducing BFD gradually, the blood concentration of CsA remained （ 161.2 ± 13）, （ 188.1 ± 16）, （204.1 ± 15） and （221.7 ± 11 ）μg·L^-1 respectively. After stopped taking BFD in 15 d, the blood concentration of CsA had a upward trend , which remained （258.4 ± 13）μg·L^-1（ P 〈 0.01）. The total bilimbin was reduced from （30 ±5.0） to （17±3.0） μmal·L^-1; the ALT was reduced from （100±50） to （30± 10）U·L^-1. The mount of urine, the urine routine test and the function remained without significant change. CONCLUSION The combination of BFD and CsA can lead to decrease the blood concentration of CsA. In order to avoid low concentrations which could lead serious kidney transplant rejection, clinical medication need to be monitored and adjusted.