CAJ | 학술논문

背景:作为抗代谢免疫抑制剂,霉酚酸酯以其低毒副作用的优点已经在实体器官移植中得到广泛应用.然而,临床上移植患者常联合用药,霉酚酸酯与其他免疫抑制剂(如环孢素 A 和他克莫司)联合使用时的药代动力学特点尚不清楚.目的:动态监测霉酚酸浓度,比较霉酚酸酯与不同免疫抑制剂联用时药代动力学特点,以探讨其最佳治疗浓度窗,指导临床个体化用药,从而提高疗效,降低其毒副反应.方法:应用 SyvaEmit-2000药物浓度检测分析仪检测肾移植受者服药(霉酚酸酯)前(C0)、服药后0.5 h(C0.5)和服药后2 h(C2)霉酚酸血浓度,并根据3个时间点的浓度值来计算0-12 h 的霉酚酸血浆浓度-时间曲线下面积值.结果与结论:入选340例肾移植受者,共检测霉酚酸3点血浆浓度-时间曲线下面积820例次,霉酚酸酯+他克莫司联合用药组574例次;霉酚酸酯+环孢素 A 联合用药组246例次.霉酚酸酯与环孢素 A 联合应用时,0-12 h 的霉酚酸血浆浓度-时间曲线下面积值显著低于霉酚酸酯与他克莫司联合应用时,差异有显著性意义(P <0.05).霉酚酸酯联用他克莫司组服药前、服药后0.5 h 霉酚酸浓度值高于霉酚酸酯联用环孢素 A 组(P <0.05),霉酚酸酯联用环孢素A 组服药后2 h 霉酚酸浓度值高于霉酚酸酯联用他克莫司组(P <0.05).霉酚酸酯联用他克莫司组服药后0.5 h 出峰的病例数高于霉酚酸酯联用环孢素 A 组(P <0.05).结果可见霉酚酸酯与不同免疫抑制剂联用时应根据相应的药代动力学特点给药,如与他克莫司联用时,应该更早地减低他克莫司剂量.三点霉酚酸血浆浓度-时间曲线下面积监测相对简便易行,在临床应用更具有可操作性.
배경:작위항대사면역억제제,매분산지이기저독부작용적우점이경재실체기관이식중득도엄범응용.연이,림상상이식환자상연합용약,매분산지여기타면역억제제(여배포소 A 화타극막사)연합사용시적약대동역학특점상불청초.목적:동태감측매분산농도,비교매분산지여불동면역억제제련용시약대동역학특점,이탐토기최가치료농도창,지도림상개체화용약,종이제고료효,강저기독부반응.방법:응용 SyvaEmit-2000약물농도검측분석의검측신이식수자복약(매분산지)전(C0)、복약후0.5 h(C0.5)화복약후2 h(C2)매분산혈농도,병근거3개시간점적농도치래계산0-12 h 적매분산혈장농도-시간곡선하면적치.결과여결론:입선340례신이식수자,공검측매분산3점혈장농도-시간곡선하면적820례차,매분산지+타극막사연합용약조574례차;매분산지+배포소 A 연합용약조246례차.매분산지여배포소 A 연합응용시,0-12 h 적매분산혈장농도-시간곡선하면적치현저저우매분산지여타극막사연합응용시,차이유현저성의의(P <0.05).매분산지련용타극막사조복약전、복약후0.5 h 매분산농도치고우매분산지련용배포소 A 조(P <0.05),매분산지련용배포소A 조복약후2 h 매분산농도치고우매분산지련용타극막사조(P <0.05).매분산지련용타극막사조복약후0.5 h 출봉적병례수고우매분산지련용배포소 A 조(P <0.05).결과가견매분산지여불동면역억제제련용시응근거상응적약대동역학특점급약,여여타극막사련용시,응해경조지감저타극막사제량.삼점매분산혈장농도-시간곡선하면적감측상대간편역행,재림상응용경구유가조작성.
BACKGROUND: As an immunosuppressant of anti-metabolites, mycophenolic acid has been widely used in organ transplantation due to its relatively low toxicity. However, its pharmacokinetic properties are unclear when combined with other immunosuppressants such as calcineurin inhibitors (tacrolimus or cyclosporine A). OBJECTIVE: To explore the optimal concentration of mycophenolic acid by dynamical y monitoring its concentration in renal transplantation recipients, comparing the pharmacokinetic properties of mycophenolic acid when combined with other immunosuppressants, in order to guide personalized medicine, thereby improving the therapeutic effect and reducing adverse effects. METHODS: The concentration of mycophenolic acid in the blood before drug administration (C0), 0.5 hour after drug administration (C0.5), and 2 hours after drug administration (C2) in the kidney recipients was determined using SyvaEmit-2000 drug concentration detection analyzer. RESULTS AND CONCLUSION: Total 820 mycophenolic acid area under the concentration time curve values were determined from 340 recipients, among which 574 mycophenolic acid area under the concentration time curve values were determined from the recipients received mycophenolate mofetil+tacrolimus and 246 from the recipients received mycophenolate mofetil+cyclosporine A respectively. In mycophenolate mofetil+cyclosporine A, the value of mycophenolic acid area under the concentration time curve was significantly lower than that in the mycophenolate mofetil+tacrolimus group, and the difference was significant (P < 0.05). The concentration of mycophenolic acid at C0 and C0.5 in the mycophenolate mofetil+tacrolimus group was higher than that in the mycophenolate mofetil+cyclosporine A group (P < 0.05), and concentration of mycophenolic acid at C2 in the mycophenolate mofetil+cyclosporine A group was higher than that in the mycophenolate mofetil+tacrolimus group (P < 0.05). Furthermore, in mycophenolate mofetil+tacrolimus group, more patients reached their peak concentration of mycophenolic acid at C0.5. The results indicated that when mycophenolate mofetil was used in combination with other immunosuppressants, the drug administration should be based on their pharmacokinetics properties and the patients might be given a lower dose of mycophenolate mofetil. Three-point mycophenolate mofetil area under the concentration-time curve method for monitoring mycophenolic acid blood concentration was simple and convenient, and could meet the needs for the clinical use.