Comparison of Clinical Application Between Tacrolimus and Cyclosporine A in Organ Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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epertment of HepatoBiliary Surgery, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China;

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Keywords：

Tacrolimus; Cyclosporine A; Pharmaceutical mechanism; Rejection response; Organ transplantation

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ObjectiveTo compare tacrolumus (FK506) with cyclosporine A (CsA) in clinical application to organ transplantation.MethodsThe literature in recent years has been reviewed and compared. ResultsFK506 was a powerful immunosuppression with a mechanism of action similar to that of CsA, but significantly superiori to CsA in terms of prophylaxis and treatment of allograft acute rejection, delay of chronic rejection, and withdrawal of steroid in early period. The cardiovascular mortality and chronic graft nephropathy (CGN),such as hypertension and hyperlipidemia were less frequently seen in FK506treated patients and FK506 also had an acceptable safety profile, including a low incidence of hypertrichosis,gingival hyperplasia and infections.However, CsA had been showed a better result in prevention of posttransplantation diabetes mellitus (PTDM ) and more economic agent than FK506. Pharmacokinetic studies showed CsA in the form of Sandimmun Neoral showed less inter an intrapatient variability than FK506.Meanwhile, the combination of MMF and FK506 or CsA has been proved effectively with excellent graft and patients survival. Conclusion FK506 and CsA are safe and effective long term maintenance immunosuppressive agents in organ transplantation with wonderful prospect.

Citation： WEI Xiaoping,LI Li. Comparison of Clinical Application Between Tacrolimus and Cyclosporine A in Organ Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(4): 415-418. doi: Copy

1.	陳實主編. 移植免疫學 [M]. 第1版.武漢：湖北科學技術出版社， 1998∶250～259.
2.	Hutchinson IV， Bagnall W, Bryce P, et al.Differences in the mode of action of cyclosporine and FK506 [J]. Transplant Proc, 1998； 30(4)∶959.
3.	Migita K, Origuchi T,Kawabe Y,et al.FK506 markedly enhances apoptosis of antigenstimulated peripheral T cells by downregulation of BclxL [J]. Transplantation, 1999; 68(7)∶1018.
4.	Appleman LJ, Berezovskaya A, Grass I, et al.CD28 costimulation mediates T cell expansion via IL2independent and IL2dependent regulation of cell cycle progression [J]. J Immunol, 2000; 164(1)∶144.
5.	Khanna AK,Hosenpud JD.Cyclosporine induces the expression of the cyclin inhibitor p21 [J]. Transplantation,1999; 67(9)∶1262.
6.	Datto MB, Yu Y, Wang XF. Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cipl/p21 promoter [J]. J Biol Chem, 1995; 270(48)∶28623.
7.	Lee JI, Ganster RW, Geller DA, et al.Cyclosporine A inhibits the expression of costimulatory molecules on in vitrogenerated dendritic cells: association with reduced nuclear translocation of nuclear factor kappa B [J]. Transplantation, 1999; 68(9)∶1255.
8.	Neuhaus P,Blumhardt G,Bechstein WO,et al.Comparison of FK506 and cyclosporinebased immunosuppression in primary orthotopic liver transplantation [J]. Transplantation, 1995; 59(1)∶31.
9.	Wiesner RH.A longterm comparison of tacrolimus(FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 Study Group [J]. Transplantation, 1998; 66(4)∶493.
10.	季曙明，殷立平，尹廣，等.他克莫司延緩移植腎功能衰竭進程的臨床研究 [J]. 中華器官移植雜志， 2000; 21(5)∶291.
11.	Wang T,Donahoe PK,Zervos AS.Specific interaction of typeⅠreceptors of the TGFβ family with the immunophilin FKBP12 [J]. Science, 1994; 265(5172)∶674.
12.	Mohamed MA, Robertson H, Booth TA, et al. TGFβ expression in renal transplant biopsies:a comparative study between cyclosporinA and tacrolimus [J]. Transplantation, 2000; 69(5)∶1002.
13.	Jain A, Mazariegos G, Kashyap R, et al. Comparative longterm evaluation of tacrolimus and cyclosporine in pediatric liver transplantation [J]. Transplantation, 2000; 70(4)∶617.
14.	Greig PD.Early steroid withdrawal following liver transplantationtwoyear followup [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.Chicago USA, 2000∶Abstract 1065.
15.	Opelz G, Wujciak T, Ritz E.Association of chronic kidney graft failure with recipient blood pressure. [J]. Kidney Int, 1998; 53(1)∶217.
16.	Stegall MD, Wachs ME, Everson G, et al.Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus [J]. Transplantation,1997; 64(12)∶1755.
17.	Pirsch JD.Tacrolimus versus cyclosporine in kidney transplantation: fiveyear survival results of the US multicenter, randomized, comparative study [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation. Chicago USA, 2000∶Abstract 10.
18.	Pirsch JD,Miller J,Deierhoi MH, et al.A comparison of tacrolimus(FK506) and cyclosporine for immunosuppression after cadavceric renal transplantation [J]. Transplantaton, 1997; 63(7)∶977.
19.	Martins L,Henriques AC,Dias L,et al.Conversion to Tacrolimus in caseproblem kidney transplant recipients under cyclosplrinebased immunosuppression [J]. Transplant Proc, 2000; 32(8)∶2636.
20.	Thorp M, Demattos A,Bennett W,et al.The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia,hirsutism and cholesterol [J]. Transplantation, 2000; 69(6)∶1218.
21.	Higgins RM,Hart P,Lam FT,et al.Conversion from tacrolimus to cyclosporine in stable renal transplant patients:safety,metabolic changes and pharmacokinetic comparison [J]. Transplantation,2000; 69(8)∶1736.
22.	Papatheodoridis GV,O’Beirne J,Mistry P, et al.Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporineinduced renal impairment: a preliminary report [J]. Transplantation, 1999; 68(1)∶155.
23.	Vanrenterghem Y,Lebranchu Y,Hene R,et al.Doubleblind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection [J]. Transplantation, 2000; 70(9)∶1352.
24.	Squifflet JP,Van Hooff JP,Vanrenterghem Y.The Benelux experience with the combination of tacrolimus and mycophenolate mofetil [J]. Transplant Proc, 1999; 31(7A)∶72s.
25.	Morales JM, Andres A, Morales E,et al.Tacrolimus,Mycophenolate mofetil and corticosteroids as primary immunosuppression after renal transplantation at the hospital 12 De Octubre,Madrid [J]. Transplant Proc, 1999; 31(7A)∶75s.
26.	Mihatsch MJ,Kyo M,Morozumi K,et al.The sideeffects of ciclosporineA and tacrolimus [J]. Clin Nephro, 1998; 49(6)∶356.
27.	Lohmann R,Langrehr JM,Klupp J,et al.Infectious complications after orthotopic liver transplantation with different immunosuppressive induction regimens [J]. Transplant Proc, 2000; 32(3)∶537.

1. 陳實主編. 移植免疫學 [M]. 第1版.武漢：湖北科學技術出版社， 1998∶250～259.
2. Hutchinson IV， Bagnall W, Bryce P, et al.Differences in the mode of action of cyclosporine and FK506 [J]. Transplant Proc, 1998； 30(4)∶959.
3. Migita K, Origuchi T,Kawabe Y,et al.FK506 markedly enhances apoptosis of antigenstimulated peripheral T cells by downregulation of BclxL [J]. Transplantation, 1999; 68(7)∶1018.
4. Appleman LJ, Berezovskaya A, Grass I, et al.CD28 costimulation mediates T cell expansion via IL2independent and IL2dependent regulation of cell cycle progression [J]. J Immunol, 2000; 164(1)∶144.
5. Khanna AK,Hosenpud JD.Cyclosporine induces the expression of the cyclin inhibitor p21 [J]. Transplantation,1999; 67(9)∶1262.
6. Datto MB, Yu Y, Wang XF. Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cipl/p21 promoter [J]. J Biol Chem, 1995; 270(48)∶28623.
7. Lee JI, Ganster RW, Geller DA, et al.Cyclosporine A inhibits the expression of costimulatory molecules on in vitrogenerated dendritic cells: association with reduced nuclear translocation of nuclear factor kappa B [J]. Transplantation, 1999; 68(9)∶1255.
8. Neuhaus P,Blumhardt G,Bechstein WO,et al.Comparison of FK506 and cyclosporinebased immunosuppression in primary orthotopic liver transplantation [J]. Transplantation, 1995; 59(1)∶31.
9. Wiesner RH.A longterm comparison of tacrolimus(FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 Study Group [J]. Transplantation, 1998; 66(4)∶493.
10. 季曙明，殷立平，尹廣，等.他克莫司延緩移植腎功能衰竭進程的臨床研究 [J]. 中華器官移植雜志， 2000; 21(5)∶291.
11. Wang T,Donahoe PK,Zervos AS.Specific interaction of typeⅠreceptors of the TGFβ family with the immunophilin FKBP12 [J]. Science, 1994; 265(5172)∶674.
12. Mohamed MA, Robertson H, Booth TA, et al. TGFβ expression in renal transplant biopsies:a comparative study between cyclosporinA and tacrolimus [J]. Transplantation, 2000; 69(5)∶1002.
13. Jain A, Mazariegos G, Kashyap R, et al. Comparative longterm evaluation of tacrolimus and cyclosporine in pediatric liver transplantation [J]. Transplantation, 2000; 70(4)∶617.
14. Greig PD.Early steroid withdrawal following liver transplantationtwoyear followup [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.Chicago USA, 2000∶Abstract 1065.
15. Opelz G, Wujciak T, Ritz E.Association of chronic kidney graft failure with recipient blood pressure. [J]. Kidney Int, 1998; 53(1)∶217.
16. Stegall MD, Wachs ME, Everson G, et al.Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus [J]. Transplantation,1997; 64(12)∶1755.
17. Pirsch JD.Tacrolimus versus cyclosporine in kidney transplantation: fiveyear survival results of the US multicenter, randomized, comparative study [C]. First Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation. Chicago USA, 2000∶Abstract 10.
18. Pirsch JD,Miller J,Deierhoi MH, et al.A comparison of tacrolimus(FK506) and cyclosporine for immunosuppression after cadavceric renal transplantation [J]. Transplantaton, 1997; 63(7)∶977.
19. Martins L,Henriques AC,Dias L,et al.Conversion to Tacrolimus in caseproblem kidney transplant recipients under cyclosplrinebased immunosuppression [J]. Transplant Proc, 2000; 32(8)∶2636.
20. Thorp M, Demattos A,Bennett W,et al.The effect of conversion from cyclosporine to tacrolimus on gingival hyperplasia,hirsutism and cholesterol [J]. Transplantation, 2000; 69(6)∶1218.
21. Higgins RM,Hart P,Lam FT,et al.Conversion from tacrolimus to cyclosporine in stable renal transplant patients:safety,metabolic changes and pharmacokinetic comparison [J]. Transplantation,2000; 69(8)∶1736.
22. Papatheodoridis GV,O’Beirne J,Mistry P, et al.Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporineinduced renal impairment: a preliminary report [J]. Transplantation, 1999; 68(1)∶155.
23. Vanrenterghem Y,Lebranchu Y,Hene R,et al.Doubleblind comparison of two corticosteroid regimens plus mycophenolate mofetil and cyclosporine for prevention of acute renal allograft rejection [J]. Transplantation, 2000; 70(9)∶1352.
24. Squifflet JP,Van Hooff JP,Vanrenterghem Y.The Benelux experience with the combination of tacrolimus and mycophenolate mofetil [J]. Transplant Proc, 1999; 31(7A)∶72s.
25. Morales JM, Andres A, Morales E,et al.Tacrolimus,Mycophenolate mofetil and corticosteroids as primary immunosuppression after renal transplantation at the hospital 12 De Octubre,Madrid [J]. Transplant Proc, 1999; 31(7A)∶75s.
26. Mihatsch MJ,Kyo M,Morozumi K,et al.The sideeffects of ciclosporineA and tacrolimus [J]. Clin Nephro, 1998; 49(6)∶356.
27. Lohmann R,Langrehr JM,Klupp J,et al.Infectious complications after orthotopic liver transplantation with different immunosuppressive induction regimens [J]. Transplant Proc, 2000; 32(3)∶537.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Comparison of Clinical Application Between Tacrolimus and Cyclosporine A in Organ Transplantation

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