1例肝移植幼儿术后服用他克莫司引起癫痫的药学服务实践
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摘要
目的:探讨他克莫司导致肝移植术后幼儿发生癫痫的原因,并通过分析药物代谢基因CYP3A5多态性及药物相互作用机制为个体化给药提供参考。方法:回顾性分析1例肝移植患儿术后使用他克莫司后出现癫痫的临床资料,检测药物基因并讨论合用药物的相互作用。结果:该患儿出现癫痫后予地西泮止痉、甘露醇降颅内压等对症治疗有效,药物代谢基因CYP3A5检测结果为CYP3A5*3/*3,依据上述结果调整给药剂量,最终患儿病情稳定。结论:肝移植患儿术后服用他克莫司可致癫痫,应及时给予对症治疗;临床药师应积极参与药物治疗,并依据其代谢酶CYP3A5基因多态性和药物相互作用为患儿制定个体化给药方案。
Objective: To explore the causes of one infant with tacrolimus-induced epilepsy after liver transplantation,and to provide reference for individualized drug administration by analyzing the polymorphism of drug metabolism gene CYP3 A5 and drug interaction mechanism. Methods: The clinical data of one infant with tacrolimus-induced epilepsy after liver transplantation was retrospectively analyzed,and the drug gene was detected and the interaction of drug combinations was discussed. Results: The infant was given diazepam for convulsion relieving and mannitol for intracranial pressure reducing after epilepsy. The detection result of drug metabolism gene CYP3 A5 was CYP3 A5* 3/* 3. The dosage was adjusted according to the above results,and the patient's condition was stable.Conclusion: Tacrolimus can induce epilepsy in children with liver transplantation,which should be given symptomatic treatment in time.Clinical pharmacists should actively participate into the drug therapy and develop individualized administration regimens for children based on the metabolic enzyme CYP3 A5 gene polymorphism and drug interactions.
Objective: To explore the causes of one infant with tacrolimus-induced epilepsy after liver transplantation,and to provide reference for individualized drug administration by analyzing the polymorphism of drug metabolism gene CYP3 A5 and drug interaction mechanism. Methods: The clinical data of one infant with tacrolimus-induced epilepsy after liver transplantation was retrospectively analyzed,and the drug gene was detected and the interaction of drug combinations was discussed. Results: The infant was given diazepam for convulsion relieving and mannitol for intracranial pressure reducing after epilepsy. The detection result of drug metabolism gene CYP3 A5 was CYP3 A5* 3/* 3. The dosage was adjusted according to the above results,and the patient's condition was stable.Conclusion: Tacrolimus can induce epilepsy in children with liver transplantation,which should be given symptomatic treatment in time.Clinical pharmacists should actively participate into the drug therapy and develop individualized administration regimens for children based on the metabolic enzyme CYP3 A5 gene polymorphism and drug interactions.
引文
[1]郑树森.肝移植[M].第2版.北京:人民卫生出版社,2012:512-513.
[2]EIDELMAN B H,ABU-ELMAGD K,WILSON J,et al. Neurologic complications of FK506[J]. Transplantation proceedings,1991,23(6):3175-3178.
[3]SEVMIS S,KARAKAYALI H,EMIROGLU R,et al. Tacrolimusrelated seizure in the early postoperative period after liver transplantation[J]. Transplantation proceedings,2007,39(4):1211-1213.
[4]BIRDWELL K A,DECKER B,BARBARINO J M,et al. Clinical pharmacogenetics implementation consortium(CPIC)guidelines for CYP3A5 genotype and tacrolimus dosing[J]. Clinical pharmacology&therapeutics,2015,98(1):19-24.
[5]王志宏,刘蕾.他克莫司的药物相互作用研究进展[J].临床合理用药杂志,2011,13(1x):117-121.
[6]PATERSON D L,SINGH N. Interactions between tacrolimus and antimicrobial agents[J]. Clinical infectious diseases,1997,25(6):1430-1440.
[7]姜楠,汪根树,李华,等.米卡芬净治疗肝移植患者侵袭性真菌感染的应用研究[J].中华肝胆外科杂志,2012,18(5):330-333.
[8]SIDDIQI N, MARFO K. Clinically significant drug-drug interaction between tacrolimus and phenobarbital:The price we pay[J]. Journal of pharmacy practice,2010,23(6):585-589.
[9]易述红,李华,杨扬,等.肝移植术后主要神经系统并发症的发生和治疗[J].南方医科大学学报,2007,27(9):1310-1313.
[10]PIZZOLATO G P, SZTAJZEL R, BURKHARDT K, et al.Cerebral vasculitis during FK506 treatment in a liver transplant patient[J]. Neurology,1998,50(4):1154-1157.
[11]TAMHANKAR M A,LESNIAK S P,NALLASAMY S,et al.Tacrolimus-induced cerebral blindness in a liver transplant patient[J]. Indian journal of ophthalmology,2016,64(7):90-97.
[12]SANER F H,SOTIROPOULOS G C,GU Y,et al. Severe neurological events following liver transplantation[J]. Archives of medical research,2007,38(1):75-79.
[13]KILINCM,BENLI S,CAN U,et al. FK506-induced fulminant leukoencephalopathy after kidney transplantation:Case report[J]. Transplantation proceedings,2002,34(4):1182-1884.
[14]中华医学会器官移植学分会肾移植学组.他克莫司在临床肾移植中的应用指南[J].中华器官移植杂志,2010,31(9):630-631.
[15]BIRDWELL K A,DECKER B,BARBARINO J M,et al.Clinical pharmacogenetics implementation consortium(CPIC)guidelines for CYP3A5 genotype and tacrolimus dosing[J].Clinical pharmacology&therapeutics,2015,98(1):19-24.
[16]朱立勤,章袁,王楠,等.肝移植患者CYP3A5和MDR1基因多态性与他克莫司浓度/剂量比的关系[J].中国新药杂志,2015,24(5):545-549.
[17]何霞,童荣生. CYP3A4和CYP3A5基因多态性对汉族肾移植患者他克莫司血药浓度的影响[J].中国药师,2013,16(4):497-501.
[18]余立冲. CYP3A5联合CYP3A4基因多态性对肾移植受者他克莫司个体化用药的指导[D].山西医科大学,2015.
[19]汪洋,张华年,徐华,等.左乙拉西坦在癫痫患儿中的群体药动学研究[J].中国新药与临床杂志,2015(3):184-190.
[20]刘文星,丁一,贾艳艳,等.左乙拉西坦片在健康人体的药代动力学[J].中国临床药理学杂志,2012,28(4):272-274.
[2]EIDELMAN B H,ABU-ELMAGD K,WILSON J,et al. Neurologic complications of FK506[J]. Transplantation proceedings,1991,23(6):3175-3178.
[3]SEVMIS S,KARAKAYALI H,EMIROGLU R,et al. Tacrolimusrelated seizure in the early postoperative period after liver transplantation[J]. Transplantation proceedings,2007,39(4):1211-1213.
[4]BIRDWELL K A,DECKER B,BARBARINO J M,et al. Clinical pharmacogenetics implementation consortium(CPIC)guidelines for CYP3A5 genotype and tacrolimus dosing[J]. Clinical pharmacology&therapeutics,2015,98(1):19-24.
[5]王志宏,刘蕾.他克莫司的药物相互作用研究进展[J].临床合理用药杂志,2011,13(1x):117-121.
[6]PATERSON D L,SINGH N. Interactions between tacrolimus and antimicrobial agents[J]. Clinical infectious diseases,1997,25(6):1430-1440.
[7]姜楠,汪根树,李华,等.米卡芬净治疗肝移植患者侵袭性真菌感染的应用研究[J].中华肝胆外科杂志,2012,18(5):330-333.
[8]SIDDIQI N, MARFO K. Clinically significant drug-drug interaction between tacrolimus and phenobarbital:The price we pay[J]. Journal of pharmacy practice,2010,23(6):585-589.
[9]易述红,李华,杨扬,等.肝移植术后主要神经系统并发症的发生和治疗[J].南方医科大学学报,2007,27(9):1310-1313.
[10]PIZZOLATO G P, SZTAJZEL R, BURKHARDT K, et al.Cerebral vasculitis during FK506 treatment in a liver transplant patient[J]. Neurology,1998,50(4):1154-1157.
[11]TAMHANKAR M A,LESNIAK S P,NALLASAMY S,et al.Tacrolimus-induced cerebral blindness in a liver transplant patient[J]. Indian journal of ophthalmology,2016,64(7):90-97.
[12]SANER F H,SOTIROPOULOS G C,GU Y,et al. Severe neurological events following liver transplantation[J]. Archives of medical research,2007,38(1):75-79.
[13]KILINCM,BENLI S,CAN U,et al. FK506-induced fulminant leukoencephalopathy after kidney transplantation:Case report[J]. Transplantation proceedings,2002,34(4):1182-1884.
[14]中华医学会器官移植学分会肾移植学组.他克莫司在临床肾移植中的应用指南[J].中华器官移植杂志,2010,31(9):630-631.
[15]BIRDWELL K A,DECKER B,BARBARINO J M,et al.Clinical pharmacogenetics implementation consortium(CPIC)guidelines for CYP3A5 genotype and tacrolimus dosing[J].Clinical pharmacology&therapeutics,2015,98(1):19-24.
[16]朱立勤,章袁,王楠,等.肝移植患者CYP3A5和MDR1基因多态性与他克莫司浓度/剂量比的关系[J].中国新药杂志,2015,24(5):545-549.
[17]何霞,童荣生. CYP3A4和CYP3A5基因多态性对汉族肾移植患者他克莫司血药浓度的影响[J].中国药师,2013,16(4):497-501.
[18]余立冲. CYP3A5联合CYP3A4基因多态性对肾移植受者他克莫司个体化用药的指导[D].山西医科大学,2015.
[19]汪洋,张华年,徐华,等.左乙拉西坦在癫痫患儿中的群体药动学研究[J].中国新药与临床杂志,2015(3):184-190.
[20]刘文星,丁一,贾艳艳,等.左乙拉西坦片在健康人体的药代动力学[J].中国临床药理学杂志,2012,28(4):272-274.