Association between cyclosporine concentrations at 2 hours post-dose and clinical outcomes in de novo lung transplant recipients
Date of Original Version
Background: The objective of this study was to investigate the relationship between cyclosporine (CsA) pharmacokinetic parameters and clinical outcomes after lung transplantation. Methods: Data from 48 lung or heart/lung transplant recipients originally recruited to a randomized, prospective clinical trial of Sandimmune vs Neoral and followed for 12 months were included in this study. CsA dosing was based on the trough concentration. CsA concentrations at 0 (C0), 2 (C2), and 6 (C6) hours post-dosing were obtained at 1, 2, 3, 4, 13, 26, 39, and 52 post-operative weeks. Based on their average C2 levels in the first post-transplant month, patients were stratified retrospectively into Low C2 (<1,000 μg/liter, n = 18), Intermediate C2 (1,000-1,500 μg/liter, n = 16) and High C2 (>1,500 μg/liter, n = 14) Groups. Results: Cyclosporine C2 was the best single-point determinant (r2 = 0.934) for area-under-the-concentration-time curve (AUC0-6 hours) compared with C0 (r2 = 0.267) or C6 (r2 = 0.304). The mean ± SD values of CsA C2 and AUC0 to 6 hours in the first year post-transplant were significantly lower in patients with >2 rejection episodes compared with those with ≤2 rejection episodes (C2: 875 ± 546 μg/liter vs 1,114 ± 633 μg/liter, p = 0.01; AUC 0-6 hours: 4,036 ± 1,904 μg × hour/liter vs 4,870 ± 2,182 μg × hour/liter; p = 0.01) whereas C0 and C6 did not differ. Patients in the Intermediate C2 Group were free from rejection episodes for a significantly longer duration (p < 0.001) and had significantly higher predicted forced expiratory volume in 1 second (%) values (p < 0.001) compared with the Low and High C2 Groups. The percentage of increase in serum creatinine concentration by the end of first month post-transplant was significantly higher in the Intermediate C2 Group (p < 0.003). Conclusions: CsA C2 concentrations correlated better with the incidence of multiple rejections after lung transplantation than did C0 or C6. C2 concentrations between 1,000 and 1,500 μg/liter within the first post-operative month may be associated with better graft outcomes and improved pulmonary function and worsened renal function. Copyright © 2005 by the International Society for Heart and Lung Transplantation.
Publication Title, e.g., Journal
Journal of Heart and Lung Transplantation
Akhlaghi, Fatemeh, Liliana Gonzalez, and Andrew K. Trull. "Association between cyclosporine concentrations at 2 hours post-dose and clinical outcomes in de novo lung transplant recipients." Journal of Heart and Lung Transplantation 24, 12 (2005). doi: 10.1016/j.healun.2005.05.005.