title: Simultaneous Characterization of Intravenous and Oral Pharmacokinetics of Lychnopholide in Rats by Transit Compartment Model.
abstract: 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 1.65 mg/kg (n = 5) and oral administration of 3.3 mg/kg (n = 3) lychnopholide in rats (0.2 ± 0.02 kg 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 0.131 l/min and intercompartmental clearance was 0.171 l/min; steady-state volume of distribution was 4.83 l. 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.
authors.affiliation: Preclinical Pharmacokinetic Laboratory, Department of Pharmacy, Maringa State University, Maringa, PR, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lachi-Silva
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Sherwin K B
authors.initials: SK
authors.lastname: Sy
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Voelkner
authors.affiliation: NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: João Paulo Barreto
authors.initials: JP
authors.lastname: de Sousa
authors.affiliation: NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: João Luis C
authors.initials: JL
authors.lastname: Lopes
authors.affiliation: NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Denise B
authors.initials: DB
authors.lastname: Silva
authors.affiliation: NPPNS (Núcleo de Pesquisa em Produtos Naturais e Sintéticos), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Norberto P
authors.initials: NP
authors.lastname: Lopes
authors.affiliation: Preclinical Pharmacokinetic Laboratory, Department of Pharmacy, Maringa State University, Maringa, PR, Brazil.
authors.forename: Elza
authors.initials: E
authors.lastname: Kimura
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.affiliation: Preclinical Pharmacokinetic Laboratory, Department of Pharmacy, Maringa State University, Maringa, PR, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Diniz
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D007783:Lactones / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; C427603:lychnopholide