Effect of compromised liver function and acute kidney injury on the pharmacokinetics of thymoquinone in a rat model / Khalid M. Alkharfy, Fahad A. Ali, Mohammad A. Alkharfy, Basit L. Jan, Mohammad Raish, Saeed Alqahtani, Ajaz Ahmad
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 AUC 0–∞ 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:50 |
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| Enthalten in: |
Xenobiotica - 50(2020), 7, Seite 858-862 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alkharfy, Khalid M. [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Themen: |
Animal model |
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| Umfang: |
1 Online-Ressource (5 p) |
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| doi: |
10.1080/00498254.2020.1745319 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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KFL01121094X |
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| 520 | |a 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 AUC 0–∞ 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 | ||
| 653 | |a Thymoquinone | ||
| 653 | |a liver dysfunction | ||
| 653 | |a kidney injury | ||
| 653 | |a pharmacokinetics | ||
| 653 | |a animal model | ||
| 653 | |a plasma protein binding | ||
| 700 | 1 | |a Ali, Fahad A. |e verfasserin |4 aut | |
| 700 | 1 | |a Alkharfy, Mohammad A. |e verfasserin |4 aut | |
| 700 | 1 | |a Jan, Basit L. |e verfasserin |4 aut | |
| 700 | 1 | |a Raish, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Alqahtani, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmad, Ajaz |e verfasserin |4 aut | |
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