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

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]

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

• Tipo de documento: Artigo Científico
• Fonte: Planta Medica; v. 81, n. 12-13, p. 1121-1127, AUG 2015.
• Citações Web of Science: 5

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
• Modalidade de apoio: 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
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários