Therapeutic drug monitoring of sirolimus: Effect of concomitant immunosuppressive therapy and optimization of drug dosing

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1345-1351
Number of pages7
JournalAmerican Journal of Transplantation
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • Drug interactions
  • Kidney transplantation
  • Sirolimus
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Therapeutic drug monitoring of sirolimus: Effect of concomitant immunosuppressive therapy and optimization of drug dosing'. Together they form a unique fingerprint.

Cite this