Effect of compromised liver function and acute kidney injury on the pharmacokinetics of thymoquinone in a rat model
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 dysfunctionThe 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; the fate of foreign compounds in biological systems - 50(2020), 7 vom: 03. Juli, Seite 858-862 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alkharfy, Khalid M [VerfasserIn] |
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| Links: |
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| Themen: |
Animal model |
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| Anmerkungen: |
Date Completed 21.07.2020 Date Revised 21.07.2020 published: Print-Electronic Citation Status MEDLINE |
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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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| PPN (Katalog-ID): |
NLM308023471 |
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| 100 | 1 | |a Alkharfy, Khalid M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of compromised liver function and acute kidney injury on the pharmacokinetics of thymoquinone in a rat model |
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| 500 | |a Date Revised 21.07.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 dysfunctionThe 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Thymoquinone | |
| 650 | 4 | |a animal model | |
| 650 | 4 | |a kidney injury | |
| 650 | 4 | |a liver dysfunction | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a plasma protein binding | |
| 650 | 7 | |a Benzoquinones |2 NLM | |
| 650 | 7 | |a thymoquinone |2 NLM | |
| 650 | 7 | |a O60IE26NUF |2 NLM | |
| 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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