Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on Phenytoin Pharmacokinetics in Beagle Dogs

The present work was designed to evaluate the effect of some commonly used herbs viz. garden cress (Lepidium sativum), black seed (Nigella sativa) and fenugreek (Trigonella foenum‐graceum) on the disposition of phenytoin after oral administration in a dog model. Phenytoin was given orally at a dose...

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Bibliographic Details
Published in:Phytotherapy research 2013-12, Vol.27 (12), p.1800-1804
Main Authors: Alkharfy, Khalid M., Al-Jenoobi, Fahad I., Al-Mohizea, Abdullah M., Al-Suwayeh, Saleh A., Khan, Rao M. A., Ahmad, Ajaz
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Bioavailability
Dogs
Drug therapy
Half-Life
Herb-Drug Interactions
herbal interaction
Lepidium sativum
Lepidium sativum - chemistry
Male
Nigella sativa
Nigella sativa - chemistry
pharmacokinetics
phenytoin
Phenytoin - pharmacokinetics
Seeds - chemistry
Trigonella - chemistry
Trigonella foenum-graceum
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Summary:The present work was designed to evaluate the effect of some commonly used herbs viz. garden cress (Lepidium sativum), black seed (Nigella sativa) and fenugreek (Trigonella foenum‐graceum) on the disposition of phenytoin after oral administration in a dog model. Phenytoin was given orally at a dose of 50 mg, and blood samples were obtained for the determination of drug's pharmacokinetic parameters. After a suitable washout period, animals were commenced on a specific herb treatment for one week. Garden cress treatment caused a modest increase in maximum observed concentration (Cmax) and terminal half‐life (T1/2λ) of phenytoin with a reduction in clearance by 33%. The effect of black seed therapy was more drastic on drug elimination and to a lesser extent on its volume of distribution at steady state (Vss) with a consequent reduction in systemic exposure measured by area under the curve (AUC0‐∞) by about 87%. The effect of fenugreek therapy resembled, albeit to a lesser extent, that of black seed with a significant reduction in AUC0‐∞ by ~72%. In addition, there was a 73% increase in Vss. Our findings suggest that the phenytoin disposition can be significantly altered by the concurrent consumption of tested herbal products. Copyright © 2013 John Wiley & Sons, Ltd.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.4947