地尔硫单用及与氨氯地平或非洛地平联用对肾移植受者他克莫司血药浓度/剂量比的影响

Effects of Only Diltiazem and Diltiazem Combined with Amlodipine or Felodipine on the Concentration / Dosage Ratio of Tacrolimus of Kidney Transplant Recipients

目的:研究地尔硫(DTZ)单用及与氨氯地平(AML)或非洛地平(FEL)联用对肾移植受者他克莫司(FK506)血药浓度/剂量比的影响。方法:选择采用FK506、吗替麦考酚酯和糖皮质激素三联免疫抑制方案并采用DTZ单用及与AML或FEL联用治疗的基因型为CYP3A5*1/*1和CYP3A5*1/*3的强代谢肾移植受者,采用微粒子酶免疫分析(MEIA)法测定患者的FK506全血谷浓度,比较单用DTZ、DTZ+AML以及DTZ+FEL对FK506血药浓度/剂量比的影响。结果:入选患者共78例。单用DTZ组患者FK506的血药浓度/剂量比显著增加,治疗第7、10、14天与使用钙拮抗药(CCBs)前比较差异均有统计学意义(P<0.05);DTZ+AML组患者FK506的血药浓度/剂量比同样显著增加(P<0.05),但作用不及单用DTZ组强;DTZ+FEL组患者FK506的血药浓度/剂量比有增加趋势,但差异无统计学意义(P>0.05)。各组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论:在免疫抑制方案基础上单用DTZ,可降低FK506的用量,显著提高其血药浓度/剂量比;在此基础上再加用1种二氢吡啶类CCBs,对FK506的血药浓度/剂量比的影响不及单用DTZ强。因此,CCBs与FK506合用,应视情况调整FK506的用量,以提高用药安全性。

OBJECTIVE：To study the effects of only diltiazem（DTZ）and DTZ combined with amlodipine（AML）or felodipine（FEL）on the concentration/dosage（C/D）ratio of tacrolimus（FK506）of kidney transplant recipients.METHODS：The immunosuppressive regimen of FK 506 combined with mycophenolate mofetil and corticosteroids was selected and kidney transplant patients with higher enzymatic of CYP3A5＊1/＊1 and CYP 3A5＊1/＊3 were treated by only DTZ and DTZ combined with AML or FEL;microparticle enzyme immunoassay（MEIA）method was used to determine the whole blood trough concentration of FK506 patients and compare the effects of the drugs in only DTZ group,DTZ＋AML group and DTZ＋FEL group on the FK506 C/D ratio.RESULTS：Totally 78 patients were enrolled.The FK506 C/D ratio of patients in only DTZ group was significantly increased,compared with before the treatment of calcium antagonists（CCBs）,there was significant difference after the treatment of 7,10 and 14d（P〉0.05）;the FK506 C/D ratio of patients in DTZ＋AML group was also significantly increased（P〉0.05）and it had weaker effects than only DTZ group;the FK506 C/D ratio of patients in DTZ＋FEL had an increasing trend,with no significant difference（P〉0.05）.There was no significant difference in the incidence of adverse reactions among groups（P〉0.05）.CONCLUSIONS：Based on the immunosuppressive regimen,only nondihydropyridine CCBs and DTZ can reduce the dosage and obviously improve the C/D ratio;based on the treatment,the effect on FK506 C/D ratio is not as strong as the only DTZ when one more nondihydropyridine CCBs is added.So,the FK506 dosage should be adjusted in the combination of CCBs and FK506 to improve the safety.