THE BENEFIT OF MONITORING CYCLOSPORINE C2 IN STABLE ASIAN TRANSPLANT PATIENTS

Abstract

P782 Aims: The benefit of cyclosporine (CyA) monitoring of AUC 0-4h has been well documented to correlate with incidence of acute rejection and acute renal dysfunction in liver and transplant patients. However, AUC 0-4h is not a practical monitoring tool in the clinical setting due to the multiple sampling of blood, making it a cumbersome and expensive management tool. The search for a single-blood sampling point that best reflects the sensitivity of AUC 0-4h is the focus of several cyclosporine monitoring research initiatives. Recent studies of cyclosporine monitoring in liver and kidney transplantation have consistently demonstrated the correlation of C2 (concentration at 2 hours post dose) and AUC 0-4 to be stronger than the correlation between C0 and AUC 0-4. Thus, it can be inferred that C2 may be a better indicator of clinical outcome and drug exposure that C0. Although many studies have proven this to be valid, a great proportion of the study population consisted of Caucasian transplant patients. Due to the fact that our center serves a large number of Asian patients, it is unknown whether the findings of published data can be applied to our patients. Furthermore, there are some reports of racial differences in CyA pharmacokinetic parameters which may affect drug monitoring. Therefore the goal of this study is to see whether the correlation between C2 and AUC 0-4 holds true in the Asian population. Methods: Eight stable liver and kidney transplant patients of Asian descent were enrolled in this prospective, open label, single-center study. Subjects were scheduled for 3 weekly visits during which whole blood samples were collected just before the administration of CyA (C0), at 2 hours (C2) and 4 hours (C4) after CyA dosing. CyA blood concentrations were measured, and trapezoidal rule was used to calculate the AUC value for each patient based on the concentrations obtained at 0, 2, and 4 hours. Pearson’s coefficient was used to analyze the correlation between the concentrations at these various intervals and the calculated AUC. Results: Seventy two serial CyA profiles at three intervals (0, 2, and 4 hours after administration of CyA) were analyzed. The correlations (r2) between CyA concentrations and the AUC0–4 at 0, 2, and 4 hours were 0.861, 0.959, and 0.666 respectively. The strongest correlation was noted for concentration at 2 hours post dose (r2 = 0.959). Conclusions: To our knowledge this is the first study to show a strong correlation between C2 and AUC0–4 in Asian transplant patients. Consequently, this suggests that monitoring CyA levels at 2 hours after CyA dosing may be superior to the conventional method of sampling at C0 in Asian transplant patients.