Correlation Between C 2 and AUC 0–4 in Renal Transplant Patients Treated With Diltiazem

Abstract

Background The area-under-the-curve (AUC) of cyclosporine (CsA) reflects exposure to the drug, but this monitoring strategy is time-consuming and not cost-effective. Recently, it has been suggested that the concentration at 2 hours after dosing (C 2) shows the best correlation with AUC. The C 2 has been replacing the trough measurement (C 0) to monitor CsA therapy, but in patients receiving diltiazem there is not much information about this issue. We investigated the correlations between C 2 and C 0 with absorption AUC over the first 4 hours (AUC 0–4) in renal stable transplant patients receiving CsA therapy with or without diltiazem. Patients and methods Ten patients (five men) of ages 23 to 68 years and 6 to 84 months after transplantation, were randomly assigned to an 8-week initial period of either diltiazem washout or controlled treatment with diltiazem. Time-concentration curves of cyclosporine were performed at the end of this period using a specific RIA measurement of blood samples. Thereafter, a crossover of the groups was performed and after another 8 weeks, a second curve was obtained. Drugs that change the pharmacokinetics of cyclosporine or diltiazem were not allowed. Results The cyclosporine daily dose was lower with diltiazem (173 ± 4 mg vs 213 ± 4 mg, P = .002), but despite a dose reduction of only 19% ± 1.5%, there was a trend to a larger AUC/dose (28 ± 5 ng · h/mL · mg vs 17 ± 2 ng · h/mL · mg, P = .1) and a trend to an increased C 2 when treatment included diltiazem (1035 ± 156 ng/mL vs 652 ± 126 ng/mL, P = NS). Moreover, we confirmed that C 2 showed the best correlation with AUC 0–4, ( r = 0.7, P = .04), a correlation that improved with diltiazem ( r = 0.9, P < .002). Conclusion C 2 is the point that correlates best with AUC 0–4 with or without diltiazem. C 2 in the presence of diltiazem was associated with a stronger, more significant correlation with AUC 0–4.