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Preclinical Pharmacokinetic Evaluation of beta-Lapachone: Characteristics of Oral Bioavailability and First-Pass Metabolism in Rats
Biomolecules & Therapeutics ; : 296-300, 2015.
Artigo em Inglês | WPRIM | ID: wpr-178031
ABSTRACT
beta-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of beta-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of beta-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of beta-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of beta-lapachone was 15.5%. The considerable degradation of beta-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of beta-lapachone may be resulted from the first-pass metabolic degradation of beta-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Plasma / Solubilidade / Farmacocinética / Disponibilidade Biológica / Administração Oral / Cromatografia Líquida de Alta Pressão / Formas de Dosagem / Administração Intravenosa / Intestinos / Fígado Limite: Animais Idioma: Inglês Revista: Biomolecules & Therapeutics Ano de publicação: 2015 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Plasma / Solubilidade / Farmacocinética / Disponibilidade Biológica / Administração Oral / Cromatografia Líquida de Alta Pressão / Formas de Dosagem / Administração Intravenosa / Intestinos / Fígado Limite: Animais Idioma: Inglês Revista: Biomolecules & Therapeutics Ano de publicação: 2015 Tipo de documento: Artigo