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Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations

2003; Springer Science+Business Media; Volume: 16; Issue: 7 Linguagem: Inglês

10.1111/j.1432-2277.2003.tb00338.x

1432-2277

Cláudia Rosso Felipe, Hélio Tedesco‐Silva, P.G.P Machado, Riberto Garcia, Silvia Regina Silva Moreira, José Osmar Medina Pestana,

Pregnancy and Medication Impact

This study analyzed early changes in trough blood cyclosporine concentrations and cyclosporine exposures after kidney trasnplantation. Seventy-two patients who received cyclosporine-based immunosuppressive therapy were intensively monitored (C0) during the first 6 months after transplantation. Full pharmacokinetic studies were performed at day 4, and months 2, 3, and 6 after transplantation. Mean steady-state, dose-adjusted trough cyclosporine blood concentrations increased from 1.1, 0.60 (day 7) to 2.0, 1.20 ng/ml per mg (day 30, P<0.01). Steadystate, dose-adjusted cyclosporine exposure parameters (C0, Cmax, AUC, Cavg, and C12) were significantly lower at day 4 than at months 2, 3, and 6 after transplantation (P<0.01). Initial cyclosporine doses produced target concentrations in only 30% of the patients at day 3. C2 was the single concentration that showed high and consistent correlation with serial AUC measurements (r2, 0.76). The incidence of biopsy-proven acute rejection was 20.5% and was not associated with ethnicity, HLA mismatch, adjunctive therapy, or blood trough cyclosporine concentrations below 200 ng/ml at day 3. Significant time-dependent increases in steadystate cyclosporine exposure occur during the first month after kidney transplantation. Due to the low relative bioavailability early after surgery, higher doses and more frequent cyclosporine dose adjustments are necessary to produce target exposures early after transplantation.