Abstract
Thymoquinone is the most biologically active constituent of Nigella sativa (black seed). A monoterpene compound chemically known as 2-methyl-5-isopropyl-1, 4-quinone. In this study, the gender-dependent pharmacokinetic behavior of thymoquinone in rats was investigated. Thymoquinone was administered orally (20 mg/kg) and intravenously (5 mg/kg) to male and female rats and blood samples were collected at specific time points. Plasma concentration-time curves were plotted and pharmacokinetic parameters were determined using the non-compartmental analysis. In addition, simulations of steady state concentrations of thymoquinone in male and female rats were performed using GastroPlus PK software. After oral administration, the maximum plasma concentration (C-max) of thymoquinone was 4.52 +/- 0.092 mu g/ml in male rats and 5.22 +/- 0.154 mu g/ml in female rats (p = 0.002). Similarly, after intravenous administration, the Cmax was 8.36 +/- 0.132 mu g/ml in males and 9.51 +/- 0.158 mu g/ml in females (p = 0.550). The area under the plasma concentration-time curve (AUC)(0-infinity) following oral dosing was 47.38 +/- 0.821 mu g/ml.h in females and 43.63 +/- 0.953 mu g/ml.h in males (p = 0.014). Pharmacokinetics and plasma concentration vs. time profiles for multiple oral doses of thymoquinone in rats were predicted using a simulation model to compare the simulation results with the experimental plasma pharmacokinetic data. The differences observed in thymoquinone pharmacokinetics between male and female rats after a single dose were not evident for the simulated steady-state parameters. The findings suggest that the gender difference does not seem to play a significant role in thymoquinone disposition at steady state. (C) 2020 Published by Elsevier B.V. on behalf of King Saud University.