Preclinical Pharmacokinetic Study and Lung Penetration of a Coumarin Extracted from Zanthoxylum tingoassuiba .
Valdeene Vieira SantosMatheus Antônio da Hora BorgesKaroline Cristina Jatobá da SilvaRafael Dos Santos CostaRenan Fernandes do Espírito SantoEudes da Silva VelozoCristiane Flora VillarrealFrancine Johansson AzeredoPublished in: Pharmaceutics (2024)
The compound 6-methoxyseselin, derived from Zanthoxylum tingoassuiba , demonstrates various therapeutic properties, including vasorelaxation, antinociceptive, anti-inflammatory, and immunomodulatory effects, along with recently discovered antiasthmatic properties. This study aimed to evaluate its preclinical pharmacokinetics and pulmonary delivery in Balb/c mice. The method involved administering the compound via inhalation and intravenous routes, followed by blood sample collection for analysis using high-performance liquid chromatography with diode array detection (HPLC-DAD). The results indicated good linearity, precision, accuracy, and stability of the compound in the biological samples. Pharmacokinetic parameters such as the rate of elimination, half-life, clearance, volume of distribution, area under the curve, and mean residence time were determined for both administration routes, showing similar profiles. The lung concentrations were notably higher than the plasma concentrations, indicating significant lung penetration. These findings suggest 6-methoxyseselin as a promising candidate for new anti-asthmatic drugs, supported by its favorable pharmacokinetic profiles and high lung penetration factors. This study represents the first exploration of the pharmacokinetics and pulmonary delivery of 6-methoxyseselin in mice, highlighting its potential for further drug development.
Keyphrases
- high performance liquid chromatography
- simultaneous determination
- anti inflammatory
- ms ms
- mass spectrometry
- pulmonary hypertension
- tandem mass spectrometry
- solid phase extraction
- high resolution
- high fat diet induced
- high dose
- stem cells
- mesenchymal stem cells
- type diabetes
- high throughput
- chronic obstructive pulmonary disease
- low dose
- bone marrow
- lung function
- loop mediated isothermal amplification