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• W4233135286 abstract "10 Cyclosporine (Cs) dosing is traditionally based on trough blood levels(C0). For Neoral®, area under the curve (AUC) based on Cs levels at 0, 1, 2, 3 and 4 hours post dose (PK0-4) correlates with AUC based on the less convenient standard 12 hour pharmacokinetics. The purpose of our study was to correlate C0 with AUC based on PK0-4, and to compare this AUC with C0 in predicting acute rejection (AR) and Cs nephrotoxicity (CsNT) after first kidney transplants.Methods: PK0-4 was done 2-4 days after initiation of Neoral® for 100 kidney transplant recipients. All received induction with continuous i.v. Cs for 1-3 days, without antibody. AUC was calculated from the PK0-4 using the parallel trapezoid rule. Neoral® dosing was based on C0, not AUC. AUC was retrospectively compared to C0 as a predictor of AR and CsNT during the first 90 days.Results: C0 correlated poorly with AUC (r2 = 0.343). C0 (mean±SEM) levels were not significantly different in 25 patients (pts) with and 75 without AR (267±28 vs 293±12 mcg/L, p=0.397). AUC was significantly lower in pts with than without AR(8628±722 vs 10502±396 mcg/L.h, p=0.021). In pts with AR in the first 15 days (19/25 pts), mean AUC was even more significantly lower than in pts without AR (7919±724 vs 10385±389 mcg/L.h, p=0.004). In logistic regression analysis only AUC (p=0.007) and delayed graft function(p=0.0006) but not HLA mismatch, source of transplant, PRA, type of immunosuppression or C0 predicted AR. AUC and C0 were both significantly higher in pts with CsNT than without CsNT (12418±977 vs 9316±374 mcg/L.h, p=0.0005; 336±22 vs 276±14 mcg/L, p=0.042), but AUC relation to CsNT was more significant. Pts with AUC in the range of 9500-11500 mcg/L.h had the lowest incidence of AR (8%, p<0.05), without significantly higher risk for CsNT. Conclusion: C0 correlates poorly with AUC based on PK0-4. Early AUC based on PK0-4 is more closely associated with AR and CsNT than is C0. Our data suggest a target AUC of 9500- 11500 mcg/L.h may provide optimal Neoral® immunosuppression. AUC determination for Neoral® is now relatively simple and convenient, and may be a more effective marker than C0 for dosing in the early post-transplant period." @default.
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• W4233135286 date "1998-06-01" @default.
• W4233135286 modified "2023-09-25" @default.
• W4233135286 title "CAN AREA UNDER THE CURVE BASED ON ABBREVIATED PHARMACOKINETICS BE USED FOR CYCLOSPORINE MICROEMULSION (NEORAL??) MONITORING IN KIDNEY TRANSPLANT RECEPIENTS?" @default.
• W4233135286 doi "https://doi.org/10.1097/00007890-199806270-00033" @default.
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