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

CONTEXT

Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the anti-SARS-CoV-2 activity of fingerroot [ (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 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 oxidation and glucuronidation, and predominantly excreted 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.