Association between cyclosporine concentrations at 2 hours post-dose and clinical outcomes in de novo lung transplant recipients

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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.

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Journal of Heart and Lung Transplantation