Effect of compromised liver function and acute kidney injury on the pharmacokinetics of thymoquinone in a rat model. (2nd July 2020)

• Record Type: Journal Article
• Authors: Alkharfy, Khalid M.; Ali, Fahad A.; Alkharfy, Mohammad A.; Jan, Basit L.; Raish, Mohammad; Alqahtani, Saeed; Ahmad, Ajaz
• Is Part Of: Xenobiotica. Volume 50:Number 7(2020:Jul.)
• Page Start: 858
• Page End: 862
• Publication Date: 2020-07-02
• Subjects: Thymoquinone -- liver dysfunction -- kidney injury -- pharmacokinetics -- animal model -- plasma protein binding; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2020.1745319
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: The current research explored the effect of hepatic and renal dysfunctions on the pharmacokinetics of thymoquinone (TQ) in a rat model. An acute kidney injury was induced using gentamicin and a liver damage was elicited using a single dose of d -galactosamine. For the pharmacokinetic studies, TQ was administered as IV injection or and PO route to rats. The concentrations of TQ and pharmacokinetic parameters were calculated using a non-compartmental analysis. The systemic clearance (Cl) of TQ after IV dosing was slightly reduced in the liver dysfunction group compared to healthy controls ( p = 0.0013). Similarly, the estimated volume of distribution at steady state (Vss) was marginally decreased ( p = 0.001). However, in rats with acute kidney injury exhibited a larger Vss as opposed to normal renal function (511.28 ± 21.03 ml/kg vs . 442.25 ± 31.43 ml/kg; p = 0.0001). Whereas oral Cl and terminal volume of distribution (Vz) of TQ were reduced by ∼50% in the liver dysfunction group ( p = 0.0001). These changes were associated with more systemic exposure as measured by AUC0–∞ in rats with compromised liver functions. The estimated plasma protein binding TQ was 99.84 ± 0.03% in healthy controls, 97.05 ± 0.57% with kidney injury rats, and 95.75 ± 0.64% in liver dysfunction The findings of the present study suggest that liver dysfunction could potentially modify the disposition of TQ administered orally, and therefore, a smaller maintenance dose is probably required to avoid accumulation.