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Pharmacokinetic evaluation of avicularin using a model-based development approach
Gabriela Amaral Buqui1, Dayana Rubio Gouvea1, Sherwin K B Sy2
1NPPNS (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.
Planta Medica
|March 18, 2015
Summary
This study projected human doses for avicularin using rat pharmacokinetic data and allometric scaling. Rat doses of 1 and 5 mg/kg correspond to human equivalent doses of 30 and 150 mg, respectively.
Area of Science:
- Pharmacology
- Drug Development
- Bioanalysis
Background:
- Avicularin's pharmacokinetic profile requires elucidation for potential therapeutic applications.
- Accurate quantification of avicularin in biological matrices is essential for pharmacokinetic studies.
Purpose of the Study:
- To determine the pharmacokinetics of avicularin in rats.
- To project human equivalent doses of avicularin using allometric scaling based on rat data.
- To develop and validate a sensitive bioanalytical method for avicularin plasma concentration determination.
Main Methods:
- Development and validation of a UPLC-MS/MS assay for avicularin quantification.
- Intravenous administration of avicularin (1 mg/kg) to rats.
- Nonlinear mixed-effects modeling to describe avicularin pharmacokinetics using a two-compartment model.
- Allometric scaling of pharmacokinetic parameters based on body weight.
- Plasma protein binding determination using the ultrafiltration method.
Main Results:
- Avicularin exhibited 64% plasma protein binding in rats.
- The pharmacokinetic data were best described by a two-compartment model.
- Avicularin was rapidly eliminated (<1 hour) and displayed linear pharmacokinetics up to 5 mg/kg.
- Rat doses of 1 and 5 mg/kg were projected to be equivalent to 30 mg and 150 mg in humans, respectively.
Conclusions:
- Allometric scaling provides a reliable method for projecting human equivalent doses of avicularin.
- The developed UPLC-MS/MS method is suitable for pharmacokinetic analysis of avicularin.
- The projected human doses can guide further clinical investigations of avicularin.
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