An open-label, single dose, safety and pharmacokinetic study of Withania somnifera root extract in healthy volunteers.

Abstract

Objectives: Withania somnifera (WS), also known as Ashwagandha, is a health-beneficial Ayurvedic medicinal plant with great potential as an adaptogen with rejuvenating and anti-aging effects. However, studies investigating pharmacokinetics (PK), safety, and tolerability of WS on humans are limited. The present study evaluated PK, safety, and tolerability of WS root extract (2.5 % total withanolides) capsules upon oral administration of two capsules of 200 mg each (total 400 mg) in healthy male and female volunteers.

Methods: An open label, single dose, clinical design comprising healthy volunteers was employed. The study evaluated PK parameters of the four bioactive constituents viz. withanoside IV, withaferin A, 12-deoxy-withastramonolide, and withanolide A in WS root extract after analysis of plasma using a validated UHPLC-MS/MS method. Further, safety and tolerability assessment for vital signs, testing for organ function, urine examination, X-ray, ECG, as well as adverse events profile were also investigated.

Results: After oral administration of 2 WS capsules (200 mg each), the participants reported normal physical, hematological, and biochemical parameters with no abnormalities in safety metrics. For the four bioactives, the exposure parameters range between 0.472 and 4.468 ng/mL (C_max), 1.000-1.416 h (T_max), and 2.051-13.319 ng/mL*h (AUC 0-t). Further, t_1/2 (1.696-4.377 h), lambda_z (0.141-0.282 L/h), Cl/F (0.065-0.954 mg/(ng/ml)/h), AUMC 0-inf_obs (21.720-80.485 ng/mL*hˆ2) and MRT 0-inf_obs (3.680-7.516 h) also differed for each bioactive.

Conclusions: The present study elucidated the PK of WS and showed that healthy male and female volunteers may safely consume WS capsules at a dose of 400 mg (2 capsules of 200 mg) without any harmful effects.