Portal de Periódicos da CAPES

Therapeutic Drug Monitoring of Sirolimus: Effect of Concomitant Immunosuppressive Therapy and Optimization of Drug Dosing

2004; Elsevier BV; Volume: 4; Issue: 8 Linguagem: Inglês

10.1111/j.1600-6143.2004.00517.x

1600-6143

Dario Cattaneo, Simona Merlini, Marisa Pellegrino, Fabiola Carrara, Stefania Zenoni, Stefano Murgia, Sara Baldelli, Flavio Gaspari, Giuseppe Remuzzi, Norberto Perico,

Electrolyte and hormonal disorders

Sirolimus (SRL) is a new immunosuppressant which shares a common metabolic pathway with several other immunosuppressive agents. This leads to potential pharmacokinetic interactions that might affect SRL blood levels with relevant clinical consequences. As a validated laboratory, 2658 SRL trough samples (corresponding to 495 kidney transplant recipients treated with different immunosuppressive regimens) from more than 40 Italian Transplant Units were analyzed. We found that dose-normalized SRL trough levels were significantly higher in patients treated with cyclosporine (CsA) and SRL (4.15 ± 2.23 ng/mL/mg SRL), compared with patients treated with mycophenolate mofetil (MMF) and SRL (3.26 ± 1.86 ng/mL/mg SRL; p < 0.01) or with MMF, steroids and SRL (2.52 ± 1.73 ng/mL/mg SRL; p < 0.01). Mean intra- and interpatient variabilities were 19% and 47%, respectively. Both parameters are significantly affected by the time postsurgery, with the first week post transplantation being associated with the greatest variability. As additional analysis, a simple dose-adjustment formula has been proposed as a useful tool to guide SRL dose changes. The proposed equation has been able to predict SRL concentration after a dose change in 73% of the tested samples. These findings suggest that different immunosuppressants significantly interfere with SRL bioavailability. Strategies aimed at reducing variability in SRL exposure may have a positive clinical impact.