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  3. Vol. 7 No. 1 (2011): IJPS_Volume 7_Issue 1 (2011)
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Vol. 7 No. 1 (2011)

January 2011

Diltiazem Co-Treatment in Renal Transplant Patients Receiving Cyclosporine with Respect to Concentration at Two Hours (C2) Cyclosporin blood level

  • Jalal Azmandian
  • Seyed Mojtaba Sohrevardi
  • Faramarz Fazeli
  • Farhad Sarrafzadeh
  • Abbas Etminan
  • Omid Savari
  • Mojtaba Ghadamzadeh

Iranian Journal of Pharmaceutical Sciences, Vol. 7 No. 1 (2011), 15 January 2011 , Page 3-6
https://doi.org/10.22037/ijps.v7.41346 Published: 2011-01-01

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Abstract

Cyclosporine (CsA) is a drug that has been used for prevention of kidney transplant rejection for many years. Diltiazem with the inhibition of cyclosporine metabolism and clearance will increase CsA concentration and CsA dose can be decreased. The aim of this study was the evaluation of diltiazem effect on CsA dose adjustment with respect to C2. Forty stable renal transplant patients who were
receiving CsA, prednisolone, mycophenolate mofetile as well as diltiazem were enrolled in the study. At first, minimum concentration of CsA (C0) and concentration within 2 h after dosing (C2) were determined in every patient. These patients were randomly assigned to an 8-week period of continued therapy with diltiazem (20 patients), or to a washout period removing diltiazem from the treatment (20 patients).
At the end of this period, CsA concentrations were measured. Thereafter, the groups underwent a crossover followed by either diltiazem washout or reinstituted treatment with diltiazem. Then C0 and C2 were measured. In each step which diltiazem was removed from patient drug regimen, CsA dose was increased by 25%. Finally, we detected that this amount of CsA dose adjustment is suitable in our patients and C0
and C2 remained in the therapeutic windows. Diltiazem co-administration with CsA will be safe and cause decreased patients drug cost.

Keywords:
  • Cyclosporine;
  • Diltiazem;
  • Kidney transplant;
  • Rejection.
  • IJPS_Volume 7_Issue 1_Pages 3-6

How to Cite

Jalal Azmandian, Seyed Mojtaba Sohrevardi, Faramarz Fazeli, Farhad Sarrafzadeh, Abbas Etminan, Omid Savari, & Mojtaba Ghadamzadeh. (2011). Diltiazem Co-Treatment in Renal Transplant Patients Receiving Cyclosporine with Respect to Concentration at Two Hours (C2): Cyclosporin blood level. Iranian Journal of Pharmaceutical Sciences, 7(1), 3–6. https://doi.org/10.22037/ijps.v7.41346
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References

[1] Quan DJ, Winter ME. Immunosuppressants: cyclosporine tacrolimus and sirolimus. In: winter ME. Basic clinical pharmacokinetics. 4th ed. Phliadelphia: Lippincott Williams and wilkins; 2004. P. 228-50.
[2] Danovitch GM. Immunosuppressive medications and protocols for kidney transplantation. In: Danovtch Gm. Handbook of kidney transplantation, 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2005. P. 72-134.
[3] Sketris IS, Methot ME, Nicol D, Belitsky P, Knox MG. Effect of calcium-channel blockers on cyclosporine clearance and use in renal transplant patients. Ann Pharmacother 1994; 28: 1227-31.
[4] Kumana CR, Tong MKL, Li CS, Lauder IJ, Lee JSK, Kou M, Walley T, Haycox A, Chan TM. Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporine. Br J Clin pharmacol 2003; 56: 670-8.
[5] Xue W, Ding X, Tian P, Pan X, Yan H, Hou J, Feng X, Xiang H, Tian X. Long-term follow-up of co-administration of diltiazem and cyclosporine in Chinese kidney transplant recipients. Ren Fail 2010; 32: 314-9.
[6] Kavukçu S, Soylu A, Türkmen M, Kasap B, Gümüştekin M, Gülay H. Two-hour post-dose cyclosporin A levels in adolescent renal transplant recipients in the late post-transplant period. Pediatr Nephrol 2004;19: 667-71.
[7] Levy G, Thervet F, Lake J, Uchida K. Patient management by Neoral C2 monitoring: an international consensus statement. Transplantation 2002; 73 (Supp): S12-8.
[8] Aros CA, Schneider Ho, Flores CA, Ardiles LG, Alruiz PA, Jerez V, Mezzano SA. Correlation between C2 and AUC 0-4 in renal transplant patients treated diltiazem. Transplant Proc 2005; 37: 1580-2.
[9] Aros CA, Ardiles LG, Schneider HO, Flores CA, Alruiz PA, Jerez VR, Mezzano SA. No gender associated differences of cyclosporine pharmacokinetics in stable renal transplant patients treated with diltiazem. Transplant Proc 2005; 37: 3364-6.
[10] Page RL, Miller GG, Lindenfeld J. Drug therapy in the heart transplant recipient: part 4: drugdrug interactions. Circulation 2005; 111: 230-9.
[11] Bunnag S, Vareesangthip K, Ong-ajyooth L.Effect of diltiazem on the pharmacokinetics of microemulsion cyclosporine A in renal transplantation. J Med Assoc Thai 2006; 89 (Suppl 2):S228-34.
[12] Ingsathit A, Sumethkul V, Chalermsanyakorn P, Jirasiritham S. Co-administration of diltiazem and cyclosporine for kidney transplant recipients: a four year follow-up study. J Med Assoc Thai 2006; 89 (Suppl 2): S235-41.
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