Pharmacokinetic Evaluation of Avicularin Using a Model-Based Development Approach

Autor(es)

Buqui, Gabriela Amaral ^[1] ; Gouvea, Dayana Rubio ^[1] ; Sy, Sherwin K. B. ^[2] ; Voelkner, Alexander ^[2] ; Singh, Ravi S. P. ^[2] ; da Silva, Denise Brentan ^[1] ; Kimura, Elza ^[3] ; Derendorf, Hartmut ^[2] ; Lopes, Norberto Peporine ^[1] ; Diniz, Andrea ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, NPPNS, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 - USA

^[3] Univ Estadual Maringa, Dept Farm, BR-87020070 Maringa, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Planta Medica; v. 81, n. 5, p. 373-381, APR 2015.
• Citações Web of Science: 4

Resumo

The aim of this study was to use the pharmacokinetic information of avicularin in rats to project a dose for humans using allometric scaling. A highly sensitive and specific bioanalytical assay to determine avicularin concentrations in the plasma was developed and validated for UPLC-MS/MS. The plasma protein binding of avicularin in rat plasma determined by the ultrafiltration method was 64%. The pharmacokinetics of avicularin in nine rats was studied following an intravenous bolus administration of 1mg/kg and was found to be best described by a two-compartment model using a nonlinear mixed effects modeling approach. The pharmacokinetic parameters were allometrically scaled by body weight and centered to the median rat weight of 0.23 kg, with the power coefficient fixed at 0.75 for clearance and 1 for volume parameters. Avicularin was rapidly eliminated from the systemic circulation within 1 h post-dose, and the avicularin pharmacokinetic was linear up to 5mg/kg based on exposure comparison to literature data for a 5-mg/kg single dose in rats. Using allometric scaling and Monte Carlo simulation approaches, the rat doses of 1 and 5 mg/kg correspond to the human equivalent doses of 30 and 150 mg, respectively, to achieve comparable plasma avicularin concentrations in humans. (AU)

• Processo FAPESP: 14/50265-3 - Metabolismo e distribuição de xenobióticos naturais e sintéticos: da compreensão dos processos reacionais à geração de imagens teciduais
• Beneficiário: Norberto Peporine Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático