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 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 (C max ) and terminal half‐life (T 1/2λ ) 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 (V ss ) with a consequent reduction in systemic exposure measured by area under the curve (AUC 0‐∞ ) by about 87%. The effect of fenugreek therapy resembled, albeit to a lesser extent, that of black seed with a significant reduction in AUC 0‐∞ by ~72%. In addition, there was a 73% increase in V ss . 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.