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

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

Author Felipe, Claudia Rosso Autor UNIFESP Google Scholar
Tedesco-Silva, Hélio Autor UNIFESP Google Scholar
Machado, Paula Goulart Pinheiro Autor UNIFESP Google Scholar
Garcia, Riberto Autor UNIFESP Google Scholar
Moreira, Silvia Regina da Silva Autor UNIFESP Google Scholar
Medina-Pestana, José Osmar Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract This study analyzed early changes in trough blood cyclosporine concentrations and cyclosporine exposures after kidney transplantation. Seventy-two patients who received cyclosporine-based immunosuppressive therapy were intensively monitored (CO) 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). Steady-state, 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 (r(2)greater than or equal to0.76). 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 steady-state 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.
Keywords kidney transplantation
cyclosporine
pharmacokinetics
therapeutic drug monitoring
Language English
Date 2003-07-01
Published in Transplant International. New York: Springer-verlag, v. 16, n. 7, p. 494-503, 2003.
ISSN 0934-0874 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 494-503
Origin http://dx.doi.org/10.1111/j.1432-2277.2003.tb00338.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000184854200007
URI http://repositorio.unifesp.br/handle/11600/27293

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