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

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.