2. Academic Validation
  3. A water-soluble preparation for intravenous administration of isorhamnetin and its pharmacokinetics in rats

A water-soluble preparation for intravenous administration of isorhamnetin and its pharmacokinetics in rats

  • Chem Biol Interact. 2024 Jun 1:396:111064. doi: 10.1016/j.cbi.2024.111064.
Giovanna Rassu 1,  Hana Kočová Vlčková 2,  Paolo Giunchedi 3,  Patrícia Dias 4,  Massimo Cossu 5,  Jana Pourová 6,  Patrícia Harčárová 7,  Zuzana Lomozová 8,  Lucie Nováková 9,  Elisabetta Gavini 10,  Přemysl Mladěnka 11
Affiliations

Affiliations

  • 1 Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23a, 07100, Sassari, Italy. Electronic address: grassu@uniss.it.
  • 2 Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: vlckh3aa@faf.cuni.cz.
  • 3 Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23a, 07100, Sassari, Italy. Electronic address: pgiunc@uniss.it.
  • 4 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: patriciaalvdias@gmail.com.
  • 5 Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23a, 07100, Sassari, Italy.
  • 6 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: pourova@faf.cuni.cz.
  • 7 Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: harcarop@faf.cuni.cz.
  • 8 Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: lomozovz@faf.cuni.cz.
  • 9 Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: novakoval@faf.cuni.cz.
  • 10 Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23a, 07100, Sassari, Italy. Electronic address: eligav@uniss.it.
  • 11 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 03, Hradec Králové, Czech Republic. Electronic address: mladenkap@faf.cuni.cz.
PMID: 38768772 DOI: 10.1016/j.cbi.2024.111064
Abstract

Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 μg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2β: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.

Keywords

Flavonoid; Isorhamnetin; Pharmacokinetics; Quercetin; Solid dispersion; Solubility.

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