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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 5
Document type: Journal article
Source: Planta Medica; v. 81, n. 12-13, p. 1121-1127, AUG 2015.
Web of Science Citations: 5
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 1.65mg/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)

FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
Grantee:Norberto Peporine Lopes
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 12/18031-7 - Application of MALDI-MS/MS in the vicenin-2 and derivatives analyses: Understanding the ionization processes to production of the images
Grantee:Denise Brentan da Silva
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 09/54098-6 - Acquisition of a mass spectrometer for the generation of images at the Mass Spectrometry Center of the University of São Paulo Ribeirão Preto School of Pharmaceutical Sciences: studies of molecular localization of biologically active substances
Grantee:Norberto Peporine Lopes
Support Opportunities: Multi-user Equipment Program