Pharmacokinetics and Metabolism of Naringin and Active Metabolite Naringenin in Rats, Dogs, Humans, and the Differences Between Species

作者：Yang Bai, Wei Peng, Cuiping Yang, Wei Zou, Menghua Liu, Hao Wu, Loudi Fan, Peibo Li, Xuan Zeng, Weiwei Su · 发表于：Frontiers in Pharmacology · 年份：2020 · DOI：10.3389/fphar.2020.00364 · 被引用次数：117 · 研究领域：Medicinal plant effects and applications、Lung Cancer Treatments and Mutations、Phytochemical compounds biological activities

BACKGROUND: Pharmacokinetics provides a scientific basis for drug product design, dosage regimen planning, understanding the body's action on the drug, and relating the time course of the drug in the body to its pharmacodynamics and/or toxic effects. Recently, naringin, a natural flavonoid, was approved for clinical trials as a first-class new drug product by the China Food and Drug Administration, owing to its nonclinical efficacy in relieving cough, reducing sputum, and low toxicity. Previous reports focused on the pharmacokinetic studies of naringin or its active metabolite naringenin in rats, which were scattered and insufficient because naringin was coadministered with mixtures such as herbs, fruits, and other traditional medicines. The purpose of this study was to evaluate the pharmacokinetics and metabolism of naringin and naringenin, following oral and intravenous administration of naringin in rats, dogs, and humans, which can be beneficial for new drug development. METHODS: Separate bioanalytical methods were developed and validated to determine the concentrations of naringin and its active metabolite naringenin in biological samples obtained from rats, dogs, and humans. Comprehensive nonclinical and clinical data were used to estimate the pharmacokinetic parameters of naringin and naringenin. Experiments included single-dose studies (oral and intravenous administration), multiple-dose studies, and an assessment of food-effects. Furthermore, the metabolism of naringi...