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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Simultaneous Characterization of Intravenous and Oral Pharmacokinetics of Lychnopholide in Rats by Transit Compartment Model

Texto completo
Autor(es):
Lachi-Silva, Larissa [1] ; Sy, Sherwin K. B. [2, 3] ; Voelkner, Alexander [2] ; Barreto de Sousa, Joao Paulo [4] ; Lopes, Joao Luis C. [4] ; Silva, Denise B. [4, 5] ; Lopes, Norberto P. [4] ; Kimura, Elza [1] ; Derendorf, Hartmut [2] ; Diniz, Andrea [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Estadual Maringa, Dept Pharm, Preclin Pharmacokinet Lab, Maringa, PR - Brazil
[2] Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 - USA
[3] Univ Estadual Maringa, Dept Stat, Biostat Master Program, Maringa, PR - Brazil
[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, NPPNS, Dept Fis & Quim, BR-14049 Ribeirao Preto, SP - Brazil
[5] Univ Fed Mato Grosso Sul UFMS, CCBS, LAPNEM Lab Prod Nat & Espectrometria Massas, Campo Grande, MS - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Planta Medica; v. 81, n. 12-13, p. 1121-1127, AUG 2015.
Citações Web of Science: 4
Resumo

The pharmacokinetic properties of a new molecular entity are important aspects in evaluating the viability of the compound as a pharmacological agent. The sesquiterpene lactone lychnopholide exhibits important biological activities. The objective of this study was to characterize the pharmacokinetics of lychnopholide after intravenous administration of 1.65mg/kg (n=5) and oral administration of 3.3mg/kg (n=3) lychnopholide in rats (0.2 +/- 0.02kg in weight) through nonlinear mixed effects modeling and non-compartmental pharmacokinetic analysis. A highly sensitive analytical method was used to quantify the plasma lychnopholide concentrations in rats. Plasma protein binding of this compound was over 99% as determined by a filtration method. A two-compartment body model plus three transit compartments to characterize the absorption process best described the disposition of lychnopholide after both routes of administration. The oral bioavailability was approximately 68%. The clearance was 0.131l/min and intercompartmental clearance was 0.171l/min; steady-state volume of distribution was 4.83l. The mean transit time for the absorption process was 9.15 minutes. No flip-flop phenomenon was observed after oral administration. The pharmacokinetic properties are favorable for further development of lychnopholide as a potential oral pharmacological agent. (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
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
Processo FAPESP: 12/18031-7 - Aplicação de MALDI-MS/MS na análise da vicenina-2 e correlatos: da compreensão dos processos ionizantes à geração de imagens
Beneficiário:Denise Brentan da Silva
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 09/54098-6 - EMU: aquisição de um espectrômetro de massas para geração de imagens na Central de Espectrometria de Massas (mass-facility) da FCFRP-USP: estudos de localização molecular de substâncias biologicamente ativas
Beneficiário:Norberto Peporine Lopes
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários