Oral Bioavailability, Tissue Distribution, Metabolism, and Excretion of Panduratin A from Boesenbergia rotunda Extract in Healthy Rats.

Abstract

Our previous studies in vitro and in vivo have shown anti-severe acute respiratory syndrome coronavirus 2 activity of fingerroot extract (Boesenbergia rotunda) and its phytochemical panduratin A. Therefore, the objective of this study was to determine the pharmacokinetic profiles of panduratin A, as a pure compound and in fingerroot extract, in rats. Male rats were randomly divided into four groups. Rats underwent intravenous administration of 4.5 mg/kg panduratin A, a single oral administration of 45 mg/kg panduratin A, or a multiple oral administration of 45 mg/kg panduratin A-consisted fingerroot extract for 7 consecutive days. The concentrations of panduratin A in plasma, tissues, and excreta were measured by using LCMS with a validated method. The rats showed no change in health status after receiving all test preparations. The absolute oral bioavailability of panduratin A administered as pure panduratin A and fingerroot extract were approximately 9% and 6%, respectively. The peak concentrations for the single oral doses of 45 mg/kg panduratin A and fingerroot extract, were 4833 ± 659 and 3269 ± 819 µg/L, respectively. Panduratin A was mostly distributed in gastrointestinal organs, with the highest tissue-to-plasma ratio in the stomach. Approximately 20-30% of unchanged panduratin A from the administered dose was detected in feces while a negligible amount was found in urine. The major metabolites of administered panduratin A were identified in feces as oxidation and dioxidation products. Panduratin A from fingerroot extract showed low oral bioavailability, good tissue distribution, and partially biotransformed before excretion via feces. These findings will assist in developing fingerroot extract as a phytopharmaceutical product for COVID-19 treatment.