Absolute oral bioavailability and possible metabolic pathway of panduratin A from Boesenbergia rotunda extract in beagle dogs

Pharm Biol. 2023 Dec;61(1):590-597. doi: 10.1080/13880209.2023.2190777.

Abstract

Context: Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the in vitro anti-SARS-CoV-2 activity of fingerroot [Boesenbergia rotunda (L.) Mansf. (Zingiberaceae)] and its phytochemical, panduratin A.

Objective: To investigate the pharmacokinetic profiles of panduratin A as a pure compound and in a fingerroot extract formulation in beagle dogs.

Materials and methods: A total of 12 healthy dogs were randomly divided into three groups, a single dose of 1 mg/kg panduratin A by intravenous and multiple doses of 5 and 10 mg/kg panduratin A fingerroot extract formulation by oral administration for seven consecutive days. The plasma concentration of panduratin A was determined by LCMS.

Results: The peak concentrations of a single dose of 5 and 10 mg/kg panduratin A fingerroot extract formulation were 12,416 ± 2,326 and 26,319 ± 8,221 µg/L, respectively. Increasing the oral dose of fingerroot extract formulation, equivalent to panduratin A 5-10 mg/kg, showed dose proportionality, with an approximately 2-fold increase in Cmax and AUC. The absolute oral bioavailability of panduratin A in the fingerroot extract formulation was approximately 7-9%. The majority of panduratin A was biotransformed into several products via oxidation and glucuronidation, and predominantly excreted via the faecal route.

Conclusion: The oral formulation of fingerroot extract was safe in beagle dogs, and increasing dose showed dose proportionality in terms of the systemic exposure of panduratin A. This information will support the phytopharmaceutical product development of fingerroot extract against the COVID-19 pandemic.

Keywords: Panduratin A; Pharmacokinetics; Zingiberaceae; fingerroot extract.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • COVID-19*
  • Dogs
  • Humans
  • Metabolic Networks and Pathways
  • Pandemics
  • Plant Extracts
  • Zingiberaceae* / chemistry

Substances

  • panduratin A
  • Plant Extracts

Grants and funding

This work was supported by the Administration and Capital Management Unit for Enhancing the Competitiveness of The Country (to Phisit Khemawoot).