Drug Design, Development and Therapy (Jul 2024)
Oral Bioavailability, Tissue Distribution, Metabolism, and Excretion of Panduratin A from Boesenbergia rotunda Extract in Healthy Rats
Abstract
Teetat Kongratanapasert,1,2 Tussapon Boonyarattanasoonthorn,3 Kittitach Supannapan,4 Suradej Hongeng,5 Phisit Khemawoot1 1Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn, Thailand; 2Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Chulalongkorn University Laboratory Animal Center, Chulalongkorn University, Bangkok, Thailand; 4Chao Phraya Abhaibhubejhr Hospital Foundation, Prachinburi, Thailand; 5Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Phisit Khemawoot, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Tel/Fax +66 28395161, Email [email protected]: 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.Aim of Study: 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.Materials and Methods: 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.Results: 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.Conclusion: 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. Keywords: pharmacokinetics, tissue distribution, biotransformation, panduratin A, Boesenbergia rotunda, COVID-19
