Effect of Diltiazem on the Pharmacokinetics of Microemulsion Cyclosporine A in Renal Transplantation
Sakarn Bunnag MD*, Kriengsak Vareesangthip MD, PhD**, Leena Ong-ajyooth MD, DrMed**
Affiliation : * Renal Division, Department of Medicine, Rajavithi Hospital ** Renal Division, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University
Objective : Diltiazem might be used as a cyclosporine A (CsA)-sparing agent. There is evidence that CsA (C2)
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 C2, in renal transplant patients.
Materials and Methods : 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, AUC0-4 and
AUC0-12. Before taking diltiazem, the correlation (r) between C0 with AUC0-4 and C0 with AUC0-12 were 0.799
and 0.871, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 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 C0 with AUC0-4 and C0 with AUC0-12 were 0.577 and
0.784, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.896, respec-
tively (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 C0 and C2 in the same patients after taking diltiazem.
Conclusion : Diltiazem slightly altered the correlation between C2 with AUC of CsA. This indicates that C2 is
the best single point blood sampling to monitor the therapeutic levels of CsA in renal transplant patients who
are taking diltiazem.
Keywords : Cyclosporine, Diltiazem, Pharmacokinetics, C2
