Significance of CYP3A5 in Individualized Immunosuppressive Treatment with Tacrolimus after Liver Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Qiyu , LI Li , LI Xiaoyan.

Department of Hepatobiliary Surgery, The First People’s Hospital of Kunming City and Affiliated Ganmei Hospital of Kunming Medical College, Kunming 650011, China;

Corresponding author：

Keywords：

Liver transplantation; Genotype; Tacrolimus; Immunosuppression; Reject reaction

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Objective To summarize the significance of CYP3A5 in individualized immunosuppressive treatment with tacrolimus (FK506) after liver transplantation.
Methods Relevant literatures about the effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in liver transplant recipients, which were published recently domestic and abroad, were reviewed and analyzed.
Results Tacrolimus was used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variation in pharmacokinetics made it difficultly to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters influenced the plasma concentration of tacrolimus. CYP3A5 genotype had an effect on the tacrolimus dose requirement in liver transplant recipients.
Conclusion Genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing liver transplantation

Citation： LIU Qiyu,LI Li,LI Xiaoyan.. Significance of CYP3A5 in Individualized Immunosuppressive Treatment with Tacrolimus after Liver Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(8): 795-797下转802. doi: Copy

1.	Braun F, Teren K, Wilms P, et al. Quality of life after liver transplantation [J]. Transplant Proc, 2009; 41(6): 25642566.
2.	Boillot O, Seket B, Dumortier J, et al. Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a fiveyear randomized prospective study [J]. Liver Transpl, 2009; 15(11): 14261434.
3.	Foroncewicz B, Mucha K, Ryszkowska E, et al. Safety and efficacy of steroidfree immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6year followup in a single center [J]. Transplant Proc, 2009; 41(8): 31033106.
4.	Fábrega E, LópezHoyos M, San Segundo D, et al. Effect of immunosuppressant blood levels on serum concentration of interleukin17 and 23 in stable liver transplant recipients [J]. Transplant Proc, 2009; 41(3): 10251027.
5.	SierraHidalgo F, MartínezSalio A, MorenoGarcía S, et al. Akinetic mutism induced by tacrolimus [J]. Clin Neuropharmacol, 2009; 32(5): 293294.
6.	Aridon P, Ragonese P, Di Benedetto N, et al. Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation [J]. Neurol Sci, 2009; 30(6): 527529.
7.	Beckebaum S, Klein C, Varghese J, et al. Renal function and cardiovascular risk profile after conversion from ciclosporin to tacrolimus: prospective study in 80 liver transplant recipients [J]. Aliment Pharmacol Ther, 2009; 30(8): 834842.
8.	Sánchez Pérez B, Aranda Narváez JM, Suárez Muoz MA, et al. Adverse effects on the lipid profile of immunosuppressive regimens: tacrolimus versus cyclosporin measured using C2 levels [J]. Transplant Proc, 2009; 41(3): 10281029.
9.	Mijiti A, Matsuno N, Takeuchi H, et al. Clinical significance of the cellular pharmacodynamics of tacrolimus in livingdonor liver transplantation [J]. Cell Transplant, 2009; 18(5): 657664.
10.	Kihara Y, Matsuno N, Mijiti A, et al. Comparative study of the cellular pharmacodynamics of calcineurin inhibitors between patients with chronic renal failure awaiting renal transplantation and cirrhosis patients awaiting liver transplantation [J]. Cell Transplant, 2009; 18(5): 639646.
11.	Wu CZ, Ni XJ, Zheng SL, et al. A fast SSPPCR method for genotyping the ATPbinding cassette subfamily B member 1 gene C3435T and G2677T polymorphisms in Chinese transplant recipients [J]. Tumori, 2009; 95(3): 338342.
12.	Terrault NA, Tran TT, Schiff E, et al. Pharmacokinetics of tacrolimus coadministered with adefovir dipivoxil to liver transplant recipients [J]. Liver Int, 2009; 29(8): 11781183.
13.	Debray D, Bernard O, Gauthier F. Pediatric liver transplantation [J]. Presse Med, 2009; 38(9): 12991306.
14.	Duvoux C, Samuel D. Hepatic transplantation [J]. Gastroenterol Clin Biol, 2009; 33(89): 868881.
15.	刘其雨, 陈刚, 温小明, 等. 再次肝移植6例报道及文献复习 [J]. 中国普外基础与临床杂志, 2009; 16(7): 540544.
16.	阳勇, 陈哲宇, 严律南, 等. 初步探讨肝内胆管结石行肝移植术的适应证 [J]. 中国普外基础与临床杂志, 2009; 16(10): 814818.
17.	Liu F, Li Y, Lan X, et al. Tacrolimus dosage requirements in living donor liver transplant recipients with smallforsize grafts [J]. World J Gastroenterol, 2009; 15(31): 39313936.
18.	Calmus Y. Immunosuppression after liver transplantation [J]. Presse Med, 2009; 38(9): 13071313.
19.	Ventura E, Bonardet A, Pageaux GP, et al. Calcineurin inhibitor determination in whole blood with the RXL Dimension analyzer: A useful tool for immunosuppressive drug monitoring [J]. Transplant Proc, 2009; 41(2): 707709.
20.	Wen J, Li L, Chen J, et al. Tripterygium wilfordii hook f increase the blood concentration of tacrolimus [J]. Transplant Proc, 2008; 40(10): 36793682.
21.	Klein A, Otto G, Krmer I. Impact of a pharmaceutical care program on liver transplant patients’ compliance with immunosuppressive medication: a prospective, randomized, controlled trial using electronic monitoring [J]. Transplantation, 2009; 87(6): 839847.
22.	Fukudo M. Individualized dosage regimen of immunosuppressive drugs based on pharmacokinetic and pharmacodynamic analysis [J]. Yakugaku Zasshi, 2007; 127(7): 10811089.
23.	Elens L, Capron A, Kerckhove VV, et al. 1199G>A and 2677G>T/A polymorphisms of ABCB1 independently affect tacrolimus concentration in hepatic tissue after liver transplantation [J]. Pharmacogenet Genomics, 2007; 17(10): 873883.
24.	Hawwa AF, McKiernan PJ, Shields M, et al. Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant [J]. Br J Clin Pharmacol, 2009; 68(3): 413421.
25.	BonhommeFaivre L, Picard V, Saliba F, et al. Effect of the ABCB1 3435C>T polymorphism on tacrolimus concentrations and dosage requirements in liver transplant recipients [J]. Am J Health Syst Pharm, 2009; 66(18): 16451651.
26.	Hosohata K, Masuda S, Katsura T, et al. Impact of intestinal CYP2C19 genotypes on the interaction between tacrolimus and omeprazole, but not lansoprazole, in adult livingdonor liver transplant patients [J]. Drug Metab Dispos, 2009; 37(4): 821826.
27.	Goto M, Masuda S, Kiuchi T, et al. CYP3A5*1carrying graft liver reduces the concentration/oral dose ratio of tacrolimus in recipients of livingdonor liver transplantation [J]. Pharmacogenetics, 2004; 14(7): 471478.
28.	BarreraPulido L, AguileraGarcía I, DocoboPérez F, et al. Clinical relevance and prevalence of polymorphisms in CYP3A5 and MDR1 genes that encode tacrolimus biotransformation enzymes in liver transplant recipients [J]. Transplant Proc, 2008; 40(9): 29492951.
29.	Hosohata K, Masuda S, Yonezawa A, et al. Absence of influence of concomitant administration of rabeprazole on the pharmacokinetics of tacrolimus in adult livingdonor liver transplant patients: a casecontrol study [J]. Drug Metab Pharmacokinet, 2009; 24(5): 458463.
30.	Provenzani A, Notarbartolo M, Labbozzetta M, et al. The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients [J]. Ann Transplant, 2009; 14(1): 2331.
31.	Weilin W, Jing J, Shusen Z, et al. Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients [J]. Liver Transpl, 2006; 12(5): 775780.
32.	Fukudo M, Yano I, Masuda S, et al. Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric livingdonor liver transplant recipients [J]. Clin Pharmacol Ther, 2006; 80(4): 331345.
33.	Yu S, Wu L, Jin J, et al. Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation [J]. Transplantation, 2006; 81(1): 4651.

1. Braun F, Teren K, Wilms P, et al. Quality of life after liver transplantation [J]. Transplant Proc, 2009; 41(6): 25642566.
2. Boillot O, Seket B, Dumortier J, et al. Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a fiveyear randomized prospective study [J]. Liver Transpl, 2009; 15(11): 14261434.
3. Foroncewicz B, Mucha K, Ryszkowska E, et al. Safety and efficacy of steroidfree immunosuppression with tacrolimus and daclizumab in liver transplant recipients: 6year followup in a single center [J]. Transplant Proc, 2009; 41(8): 31033106.
4. Fábrega E, LópezHoyos M, San Segundo D, et al. Effect of immunosuppressant blood levels on serum concentration of interleukin17 and 23 in stable liver transplant recipients [J]. Transplant Proc, 2009; 41(3): 10251027.
5. SierraHidalgo F, MartínezSalio A, MorenoGarcía S, et al. Akinetic mutism induced by tacrolimus [J]. Clin Neuropharmacol, 2009; 32(5): 293294.
6. Aridon P, Ragonese P, Di Benedetto N, et al. Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation [J]. Neurol Sci, 2009; 30(6): 527529.
7. Beckebaum S, Klein C, Varghese J, et al. Renal function and cardiovascular risk profile after conversion from ciclosporin to tacrolimus: prospective study in 80 liver transplant recipients [J]. Aliment Pharmacol Ther, 2009; 30(8): 834842.
8. Sánchez Pérez B, Aranda Narváez JM, Suárez Muoz MA, et al. Adverse effects on the lipid profile of immunosuppressive regimens: tacrolimus versus cyclosporin measured using C2 levels [J]. Transplant Proc, 2009; 41(3): 10281029.
9. Mijiti A, Matsuno N, Takeuchi H, et al. Clinical significance of the cellular pharmacodynamics of tacrolimus in livingdonor liver transplantation [J]. Cell Transplant, 2009; 18(5): 657664.
10. Kihara Y, Matsuno N, Mijiti A, et al. Comparative study of the cellular pharmacodynamics of calcineurin inhibitors between patients with chronic renal failure awaiting renal transplantation and cirrhosis patients awaiting liver transplantation [J]. Cell Transplant, 2009; 18(5): 639646.
11. Wu CZ, Ni XJ, Zheng SL, et al. A fast SSPPCR method for genotyping the ATPbinding cassette subfamily B member 1 gene C3435T and G2677T polymorphisms in Chinese transplant recipients [J]. Tumori, 2009; 95(3): 338342.
12. Terrault NA, Tran TT, Schiff E, et al. Pharmacokinetics of tacrolimus coadministered with adefovir dipivoxil to liver transplant recipients [J]. Liver Int, 2009; 29(8): 11781183.
13. Debray D, Bernard O, Gauthier F. Pediatric liver transplantation [J]. Presse Med, 2009; 38(9): 12991306.
14. Duvoux C, Samuel D. Hepatic transplantation [J]. Gastroenterol Clin Biol, 2009; 33(89): 868881.
15. 刘其雨, 陈刚, 温小明, 等. 再次肝移植6例报道及文献复习 [J]. 中国普外基础与临床杂志, 2009; 16(7): 540544.
16. 阳勇, 陈哲宇, 严律南, 等. 初步探讨肝内胆管结石行肝移植术的适应证 [J]. 中国普外基础与临床杂志, 2009; 16(10): 814818.
17. Liu F, Li Y, Lan X, et al. Tacrolimus dosage requirements in living donor liver transplant recipients with smallforsize grafts [J]. World J Gastroenterol, 2009; 15(31): 39313936.
18. Calmus Y. Immunosuppression after liver transplantation [J]. Presse Med, 2009; 38(9): 13071313.
19. Ventura E, Bonardet A, Pageaux GP, et al. Calcineurin inhibitor determination in whole blood with the RXL Dimension analyzer: A useful tool for immunosuppressive drug monitoring [J]. Transplant Proc, 2009; 41(2): 707709.
20. Wen J, Li L, Chen J, et al. Tripterygium wilfordii hook f increase the blood concentration of tacrolimus [J]. Transplant Proc, 2008; 40(10): 36793682.
21. Klein A, Otto G, Krmer I. Impact of a pharmaceutical care program on liver transplant patients’ compliance with immunosuppressive medication: a prospective, randomized, controlled trial using electronic monitoring [J]. Transplantation, 2009; 87(6): 839847.
22. Fukudo M. Individualized dosage regimen of immunosuppressive drugs based on pharmacokinetic and pharmacodynamic analysis [J]. Yakugaku Zasshi, 2007; 127(7): 10811089.
23. Elens L, Capron A, Kerckhove VV, et al. 1199G>A and 2677G>T/A polymorphisms of ABCB1 independently affect tacrolimus concentration in hepatic tissue after liver transplantation [J]. Pharmacogenet Genomics, 2007; 17(10): 873883.
24. Hawwa AF, McKiernan PJ, Shields M, et al. Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant [J]. Br J Clin Pharmacol, 2009; 68(3): 413421.
25. BonhommeFaivre L, Picard V, Saliba F, et al. Effect of the ABCB1 3435C>T polymorphism on tacrolimus concentrations and dosage requirements in liver transplant recipients [J]. Am J Health Syst Pharm, 2009; 66(18): 16451651.
26. Hosohata K, Masuda S, Katsura T, et al. Impact of intestinal CYP2C19 genotypes on the interaction between tacrolimus and omeprazole, but not lansoprazole, in adult livingdonor liver transplant patients [J]. Drug Metab Dispos, 2009; 37(4): 821826.
27. Goto M, Masuda S, Kiuchi T, et al. CYP3A5*1carrying graft liver reduces the concentration/oral dose ratio of tacrolimus in recipients of livingdonor liver transplantation [J]. Pharmacogenetics, 2004; 14(7): 471478.
28. BarreraPulido L, AguileraGarcía I, DocoboPérez F, et al. Clinical relevance and prevalence of polymorphisms in CYP3A5 and MDR1 genes that encode tacrolimus biotransformation enzymes in liver transplant recipients [J]. Transplant Proc, 2008; 40(9): 29492951.
29. Hosohata K, Masuda S, Yonezawa A, et al. Absence of influence of concomitant administration of rabeprazole on the pharmacokinetics of tacrolimus in adult livingdonor liver transplant patients: a casecontrol study [J]. Drug Metab Pharmacokinet, 2009; 24(5): 458463.
30. Provenzani A, Notarbartolo M, Labbozzetta M, et al. The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients [J]. Ann Transplant, 2009; 14(1): 2331.
31. Weilin W, Jing J, Shusen Z, et al. Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients [J]. Liver Transpl, 2006; 12(5): 775780.
32. Fukudo M, Yano I, Masuda S, et al. Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric livingdonor liver transplant recipients [J]. Clin Pharmacol Ther, 2006; 80(4): 331345.
33. Yu S, Wu L, Jin J, et al. Influence of CYP3A5 gene polymorphisms of donor rather than recipient to tacrolimus individual dose requirement in liver transplantation [J]. Transplantation, 2006; 81(1): 4651.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Significance of CYP3A5 in Individualized Immunosuppressive Treatment with Tacrolimus after Liver Transplantation

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