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Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients.
Ferreira, Pâmela C Lukasewicz; Thiesen, Flavia Valladao; de Araujo, Thaina Tavares; D'Ávila, Domingos Otávio; Gadonski, Giovani; de Oliveira, Carmem Silvana A; Zimmer, Aline Rigon; Fröehlich, Pedro Eduardo.
Afiliação
  • Ferreira PCL; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil. pamlukasewicz@gmail.com.
  • Thiesen FV; Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6682, Porto Alegre, RS, 90619-900, Brazil.
  • de Araujo TT; Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6682, Porto Alegre, RS, 90619-900, Brazil.
  • D'Ávila DO; Centro de Pesquisa Clínica, Hospital São Lucas da PUC, Av. Ipiranga 6690, Porto Alegre, RS, 90619-900, Brazil.
  • Gadonski G; Clínica Medica, Hospital São Lucas da PUC, Av. Ipiranga 6690, Porto Alegre, RS, 90619-900, Brazil.
  • de Oliveira CSA; Centro de Pesquisa Clínica, Hospital São Lucas da PUC, Av. Ipiranga 6690, Porto Alegre, RS, 90619-900, Brazil.
  • Zimmer AR; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.
  • Fröehlich PE; Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.
Eur J Clin Pharmacol ; 75(4): 553-559, 2019 Apr.
Article em En | MEDLINE | ID: mdl-30610275
PURPOSE: Mycophenolic acid is one of the most used immunosuppressive drugs in solid organ transplant treatments in the world. Developing a highly sensitive analytical method to analyse the drug and its metabolites in oral fluid and plasma is important to evaluate the possibility of using oral fluid as a biological matrix in therapeutic drug monitoring, instead of plasma. METHOD: The liquid chromatography coupled to mass spectrometry (LC-MS) method was developed and validated for determining mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) in oral fluid and plasma, with both matrices presenting a detection limit of 1 ng/mL for MPA and 5 ng/mL for MPAG. Both analytes were analysed after a simple protein precipitation procedure. Transplanted-kidney samples of oral fluid and blood were collected from 13 patients that were hospitalised and kept at - 80 °C until analyses. RESULTS: The proposed method was linear in the concentration range of 5-500 ng/mL for MPA and 10-500 ng/mL for MPAG, with correlation coefficients (r) between 0.9925 and 0.9973. It was then applied to samples collected from kidney-transplanted patients and used for calculation of pharmacokinetics parameters. CONCLUSION: After comparing plasma and oral fluid concentrations as well as performing a non-compartmental pharmacokinetic analysis of the average curves, it is possible to suggest that oral fluid concentration may be used as an alternative for MPA and MPAG monitoring in kidney transplant patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saliva / Transplante de Rim / Glucuronídeos / Ácido Micofenólico Limite: Humans Idioma: En Revista: Eur J Clin Pharmacol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saliva / Transplante de Rim / Glucuronídeos / Ácido Micofenólico Limite: Humans Idioma: En Revista: Eur J Clin Pharmacol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Alemanha