Effect of diltiazem on the pharmacokinetics of microemulsion cyclosporine A in renal transplantation

Abstract

Objective: Diltiazem might be used as a cyclosporine A (CsA)-sparing agent. There is evidence that CsA (C 2) level is the best single point blood sampling for monitoring the CsA level. The authors, therefore, studied the effect of diltiazem on the pharmacokinetics (PK) of CsA, including C 2, in renal transplant patients. Material and Method: Twenty-five CsA-treated renal transplant patients, with neither diseases nor agents that alter the PK of CsA, were enrolled in the present study. The PK of CsA was studied in all patients before and 2 weeks after taking diltiazem. Results: The area under the concentration-time curve (AUC) of CsA was obtained by 2 methods, AUC 0-4 and AUC 0-12. Before taking diltiazem, the correlation (r) between C 0 with AUC 0-4 and C 0 with AUC 0-12 were 0.799 and 0.871, respectively (p = 0.01), r between C 2 with AUC 0-4 and C 2 with AUC 0-12 were 0.988 and 0.956, respectively (p = 0.01). Time to maximum concentration (Tmax) of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. After two weeks of taking diltiazem, r between C 2 with AUC 0-4 and C 0 with AUC 0-12 were 0.577 and 0.784, respectively (p = 0.01), r between C 2 with AUC 0-4 and C 2 with AUC 0-12 were 0.988 and 0.896, respectively (p = 0.01). Tmax of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. The dosage of CsA could be reduced by 25.8% to maintain the same levels of C 0 and C 2 in the same patients after taking diltiazem. Conclusion: Diltiazem slightly altered the correlation between C 2 with AUC of CsA. This indicates that C 2 is the best single point blood sampling to monitor the therapeutic levels of CsA in renal transplant patients who are taking diltiazem.