Gender effect on the pharmacokinetics of thymoquinone: Preclinical investigation and in silico modeling in male and female rats.
Saudi Pharm J
; 28(4): 403-408, 2020 Apr.
Article
em En
| MEDLINE
| ID: mdl-32273798
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 (20â¯mg/kg) and intravenously (5â¯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 (Cmax) of thymoquinone was 4.52⯱â¯0.092⯵g/ml in male rats and 5.22⯱â¯0.154⯵g/ml in female rats (pâ¯=â¯0.002). Similarly, after intravenous administration, the Cmax was 8.36⯱â¯0.132⯵g/ml in males and 9.51⯱â¯0.158⯵g/ml in females (pâ¯=â¯0.550). The area under the plasma concentration-time curve (AUC)0-∞ following oral dosing was 47.38⯱â¯0.821⯵g/ml·h in females and 43.63⯱â¯0.953⯵g/ml·h in males (pâ¯=â¯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.
AUC, area under plasma concentration-time curve; AUMC, area under the first moment curve; CMC, carboxy methyl cellulose; Cl, total clearance; Cmax, maximum plasma concentration; GastroPlus PK simulations; I.V., intravenous; MRT, mean residence time; Male and female rats; P.O., oral; Pharmacokinetics; Plasma; T1/2, elimination half-life; THQ, Thymoquinone; Thymoquinone; Tmax, time to maximum concentration; Vss, volume of distribution at steady state; Vz, volume of distribution z; λz, terminal elimination rate constant
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Saudi Pharm J
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Arábia Saudita