Pharmacokinetic Advantages of Two-Hour Post-Dose Cyclosporin A Level for the Therapeutic Drug Monitoring in Stable Chinese Kidney Transplant Recipients

Abstract

Background: Recent studies in Caucasian patients show that 2-hour post-dose cyclosporin A level (C2) monitoring has excellent correlation with the actual drug exposure and risk of rejection. However, the reliability of using C2 in stable Chinese renal transplant patients is unknown. Methods: Forty-nine stable Chinese renal transplant patients receiving microemulsion cyclosporin A (Neoral^®) as part of their immunosuppressive therapy were recruited. Area under the time-concentration curve (AUC) was determined from whole blood cyclosporin A level taken at 0, 1, 2, 4 and 6 h post-dose at time 0 month. Cyclosporin A levels were repeated at 0, 1 and 2 h post-dose at 1 and 2 months later to determine the intra-individual variation at these specific time points. Results: The average duration of transplantation was 77 ± 42 months, with average daily cyclosporin dosage of 200 ± 43 mg in two divided doses. AUC has excellent correlations with cyclosporin A level at 1 h (C1) and 2 h (C2) (r = 0.81 and 0.82 respectively, p < 0.001 for both). The correlation between AUC and trough cyclosporin A level (C0) was statistically significant but only modest (r = 0.52, p < 0.001). On the other hand, the intra-individual coefficient of variation (CV_w) of C1 was significantly larger than that of C2 (34.4 ± 24.2 vs. 15.9 ± 8.3%, p < 0.0001). Conclusion: We conclude that C2 level has favorable pharmacokinetic properties for therapeutic drug monitoring in stable Chinese transplant recipients. Both C1 and C2 have excellent correlation with AUC, but the intra-individual variability of C2 is much lower than that of C1.