Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus

Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus

Autor Park, Sung-In Autor UNIFESP Google Scholar
Felipe, Claudia R. Autor UNIFESP Google Scholar
Pinheiro-Machado, Paula G. Autor UNIFESP Google Scholar
Garcia, Riberto Autor UNIFESP Google Scholar
Fernandes, Fernanda B. Autor UNIFESP Google Scholar
Casarini, Dulce E. Autor UNIFESP Google Scholar
Tedesco-Silva, Helio Autor UNIFESP Google Scholar
Medina-Pestana, Jose O. Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo This study was conducted to evaluate time-dependent pharmacokinetic changes and drug interactions over the first 6 months after transplantation in kidney transplant recipients receiving tacrolimus (TAC), prednisone (PRED) and mycophenolate mofetil (MMF) or sirolimus (SRL). Pharmacokinetic assessments were carried out at day 7 and months 1, 3, and 6 in kidney transplant recipients receiving TAC plus PRED with either MMF (2 g/day, n = 13) or SRL (15 mg loading dose, 5 mg for 7 days followed by 2 mg/day, n = 12). There were no differences in the main demographic characteristics or in mean PRED doses during the first 6 months after transplant. From day 7 to month 6, there was a 65% increase in TAC dose corrected exposure (dose corrected area under the curve; AUC) in patients receiving MMF (P = 0.005) and a 59% increase in TAC dose corrected exposure in patients receiving SRL (P = 0.008). From day 7 to month 6, there was a 72% increase in mycophenolate dose corrected exposure (P = 0.001) and a 65% increase in SRL dose corrected exposure (P = 0.008). TAC dose corrected exposure was 23% lower in patients receiving SRL compared with MMF (P = 0.012) on average over the study period. PRED dose reduction was associated with increase in TAC (in patients receiving SRL, P = 0.040) and mycophenolic acid (MPA) (P = 0.070) drug exposures. Tercile distribution of TAC drug exposure showed a positive correlation with mean SRL exposures (P = 0.016). Conversely, tercile distribution of SRL drug exposure showed a positive correlation with mean TAC exposures (P = 0.004). Time-dependent increases in TAC, MPA and SRL drug exposures occur up to 6 months after transplantation. Drug-to-drug interactions indicate that intense therapeutic drug monitoring is required to avoid under-or over-immunosuppression.
Assunto drug interaction
kidney transplantation
mycophenolate mofetil
pharmacokinetics
prednisone
sirolimus
tacrolimus
Idioma Inglês
Data 2009-02-01
Publicado em Fundamental & Clinical Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 23, n. 1, p. 137-145, 2009.
ISSN 0767-3981 (Sherpa/Romeo, fator de impacto)
Editor Wiley-Blackwell
Extensão 137-145
Fonte http://dx.doi.org/10.1111/j.1472-8206.2008.00644.x
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000264373100015
URI http://repositorio.unifesp.br/handle/11600/31309

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