Conclusion
The results of this study highlight the importance of withanolide glycosides in improving the pharmacokinetics of WS extracts. Owing to its superior pharmacokinetic profile, WS-35, with 35% withanolide glycosides, is a promising candidate for further studies on Withania somnifera. Clinical
Methods
This randomized, double-blind, single-dose crossover study of 16 healthy human volunteers evaluated the acute oral bioavailability of withanolides and the bioequivalence of two WS extracts, WS-35 and WS-2.5. WS-35 was standardized to total withanolides not less than 40% comprising not less than 35% withanolide glycosides and WS-2.5 was standardized to 2.5% withanolides. The clinical dosages were normalized to 185 mg of total withanolide in each extract at the bioequivalent dosages. The pharmacokinetic parameters of withanolide A, withanoside IV, withaferin A, and total withanolides were quantified in the blood plasma using a validated LC-MS/MS method.
Results
The half-life, C-max, and mean residence time of the total withanolides were 5.18, 5.62 and 4.13 times significantly higher and had lower systemic clearance with WS-35 than with WS-2.5 extract. Considering the plasma AUC 0-inf of total withanolides per mg of each WS extract administered orally, WS-35 was 280.74 times more bioavailable than WS-2.5.
Trial registration
CTRI/2020/10/028397 [registered on:13/10/2020] (Trial prospectively registered) http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=42149&EncHid=&userName=CTRI/2020/10/028397.