A clinical pharmacokinetic study of tacrolimus and sirolimus combination immunosuppression comparing simultaneous to separated administration

Vivian C. McAlister, Kamran Mahalati, Kevork M. Peltekian, Albert Fraser, Allan S. MacDonald

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

87 Citas (Scopus)

Resumen

The pharmacokinetic (PK) interaction between tacrolimus (TAC) and sirolimus (SRL), similarly structured immunosuppressive compounds that share binding proteins, is unknown. The combination of SRL with cyclosporin (CsA) has been studied, and a 4-hour interval between dosing of the two drugs is recommended even though it is inconvenient for patients and may affect compliance. Twenty-five liver and kidney-pancreas transplant recipients treated with a combination of SRL and low-dose TAC completed full PK studies while being treated with 4-hour interval dosing (ID) and then with simultaneous dosing. Whole blood was sampled for immunoassay measurement of TAC and SRL levels. Blood concentration/dose ratios of SRL and TAC varied between patients by a factor of 8 and 5, respectively, but correlation between trough concentration levels (C0) and drug exposure area under the concentration-time curve (AUC) was excellent (TAC: r2 = 0.82; SRL: r2 = 0.83). Neither PK profiles of SRL nor those of TAC were altered by simultaneous administration. Dose-corrected AUC and C0 of TAC correlated with SRL (r2 = 0.8 and 0.8, respectively). Bone marrow suppression and nephrotoxicity were not enhanced nor were any new toxicities observed when TAC and SRL were used in combination. These data confirm that simultaneous dosing of TAC and SRL after transplantation is safe and that trough level monitoring is adequate to control therapy.

Idioma originalEnglish
Páginas (desde-hasta)346-350
Número de páginas5
PublicaciónTherapeutic Drug Monitoring
Volumen24
N.º3
DOI
EstadoPublished - 2002
Publicado de forma externa

ASJC Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

PubMed: MeSH publication types

  • Clinical Trial
  • Journal Article

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