• 昆明市第一人民醫(yī)院暨昆明醫(yī)學(xué)院附屬甘美醫(yī)院肝膽外科（昆明 650011）;

目的 總結(jié)CYP3A5在肝移植術(shù)后他克莫司個體化治療中的意義。
方法 復(fù)習(xí)、分析近年來有關(guān)肝移植患者CYP3A5基因多態(tài)性對他克莫司藥代動力學(xué)影響的文獻(xiàn)。
結(jié)果 他克莫司可以有效預(yù)防肝移植的排斥反應(yīng)。藥代動力學(xué)中狹窄的有效藥物濃度范圍和個體差異使其很難確定針對所有患者的固定劑量，藥物代謝酶和轉(zhuǎn)運(yùn)子的基因多態(tài)性影響著他克莫司的血藥濃度。CYP3A5基因分型影響著肝移植受體的他克莫司需要量。
結(jié)論 CYP3A5基因分型可能為優(yōu)化肝移植患者的免疫抑制治療提供幫助。

引用本文： 劉其雨,李立,李曉延. CYP3A5在肝移植術(shù)后他克莫司個體化治療中的意義. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(8): 795-797下轉(zhuǎn)802. doi: 復(fù)制

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. 劉其雨, 陳剛, 溫小明, 等. 再次肝移植6例報(bào)道及文獻(xiàn)復(fù)習(xí) [J]. 中國普外基礎(chǔ)與臨床雜志, 2009; 16(7): 540544.
16. 陽勇, 陳哲宇, 嚴(yán)律南, 等. 初步探討肝內(nèi)膽管結(jié)石行肝移植術(shù)的適應(yīng)證 [J]. 中國普外基礎(chǔ)與臨床雜志, 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. 1. Braun F, Teren K, Wilms P, et al. Quality of life after liver transplantation [J]. Transplant Proc, 2009; 41(6): 25642566.
  2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 13. Debray D, Bernard O, Gauthier F. Pediatric liver transplantation [J]. Presse Med, 2009; 38(9): 12991306.
  14. 14. Duvoux C, Samuel D. Hepatic transplantation [J]. Gastroenterol Clin Biol, 2009; 33(89): 868881.
  15. 15. 劉其雨, 陳剛, 溫小明, 等. 再次肝移植6例報(bào)道及文獻(xiàn)復(fù)習(xí) [J]. 中國普外基礎(chǔ)與臨床雜志, 2009; 16(7): 540544.
  16. 16. 陽勇, 陳哲宇, 嚴(yán)律南, 等. 初步探討肝內(nèi)膽管結(jié)石行肝移植術(shù)的適應(yīng)證 [J]. 中國普外基礎(chǔ)與臨床雜志, 2009; 16(10): 814818.
  17. 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. 18. Calmus Y. Immunosuppression after liver transplantation [J]. Presse Med, 2009; 38(9): 13071313.
  19. 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. 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. 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. 22. Fukudo M. Individualized dosage regimen of immunosuppressive drugs based on pharmacokinetic and pharmacodynamic analysis [J]. Yakugaku Zasshi, 2007; 127(7): 10811089.
  23. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.