Your browser doesn't support javascript.
loading
Population Pharmacokinetic Modeling to Describe the Total Plasma and Free Brain Levels of Fluconazole in Healthy and Cryptococcus neoformans Infected Rats: How Does the Infection Impact the Drug's Levels on Biophase?
Alves, Izabel Almeida; Staudt, Keli Jaqueline; Carreño, Fernando Olinto; de Araujo Lock, Graziela; de Miranda Silva, Carolina; Rates, Stela Maris Kuze; Dalla Costa, Teresa; De Araujo, Bibiana Verlindo.
Afiliação
  • Alves IA; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
  • Staudt KJ; Medical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga 2752, office 407, Porto Alegre, RS, 90610-000, Brazil.
  • Carreño FO; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
  • de Araujo Lock G; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
  • de Miranda Silva C; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
  • Rates SMK; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
  • Dalla Costa T; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
  • De Araujo BV; Pharmaceutical Sciences Graduate Program of Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil. bibiana.araujo@ufrgs.br.
Pharm Res ; 35(7): 132, 2018 Apr 27.
Article em En | MEDLINE | ID: mdl-29704215
PURPOSE: The present work aimed to evaluate the influence of experimental meningitis caused by C. neoformans on total plasma and free brain concentrations of fluconazole (FLC) in Wistar rats. METHOD: The infection was induced by the administration of 100 µL of inoculum (1.105 CFU) through the tail vein. Free drug in the brain was assessed by microdialisys (µD). Blood and µD samples were collected at pre-determined time points up to 12 h after intravenous administration of FLC (20 mg/kg) to healthy and infected rats. The concentration-time profiles were analyzed by non-compartmental and population pharmacokinetics approaches. RESULTS: A two-compartmental popPK model was able to simultaneously describe plasma and free drug concentrations in the brain for both groups investigated. Analysis of plasma and µD samples showed a better FLC distribution on the brain of infected than healthy animals (1.04 ± 0.31 vs 0.69 ± 0.14, respectively). The probability of target attainment was calculated by Monte Carlo simulations based on the developed popPK model for 125 mg/kg dose for rats and 400-2000 mg for humans. CONCLUSIONS: FLC showed a limited use in monotherapy to the treatment of criptoccocosis in rats and humans to value of MIC >8 µg/mL.
Assuntos
Palavras-chave
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: Encéfalo / Fluconazol / Criptococose / Cryptococcus neoformans / Modelos Biológicos / Antifúngicos Tipo de estudo: Health_economic_evaluation Limite: Animals Idioma: En Revista: Pharm Res Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
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: Encéfalo / Fluconazol / Criptococose / Cryptococcus neoformans / Modelos Biológicos / Antifúngicos Tipo de estudo: Health_economic_evaluation Limite: Animals Idioma: En Revista: Pharm Res Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos