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Planta Med 2015; 81(12/13): 1121-1127
DOI: 10.1055/s-0035-1546214
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

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

Larissa Lachi-Silva
1   Preclinical Pharmacokinetic Laboratory, Department of Pharmacy, Maringa State University, Maringa, PR, Brazil
,
Sherwin K. B. Sy
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
3   Biostatistics Master Program, Department of Statistics, Maringa State University, Maringa, PR, Brazil
,
Alexander Voelkner
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
,
João Paulo Barreto de Sousa
4   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
,
João Luis C. Lopes
4   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
,
Denise B. Silva
4   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
5   LAPNEM (Laboratório de Produtos Naturais e Espectrometria de Massas), Centro de Ciências Biológicas e da Saúde (CCBS), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil
,
Norberto P. Lopes
4   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
,
Elza Kimura
1   Preclinical Pharmacokinetic Laboratory, Department of Pharmacy, Maringa State University, Maringa, PR, Brazil
,
Hartmut Derendorf
2   Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA
,
Andrea Diniz
1   Preclinical Pharmacokinetic Laboratory, Department of Pharmacy, Maringa State University, Maringa, PR, Brazil
› Author Affiliations
Further Information

Publication History

received 11 March 2015
revised 19 May 2015

accepted 25 May 2015

Publication Date:
28 July 2015 (online)

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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.

Key words

lychnopholide - pharmacokinetic - transit compartment - model-based development - pharmacognosy - population pharmacokinetic

* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.


 

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