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.