Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs

Context: Herb-drug interactions are a serious problem especially for drugs with a narrow therapeutic index, taking into consideration that herbal medicines are commonly used in various parts of the world. Objective: The present study investigates the effect of fenugreek, garden cress, and black seed on the pharmacokinetics of theophylline in beagle dogs. Materials and methods: Beagle dogs received theophylline (200 mg) orally and blood samples were withdrawn at different time intervals (0.33, 0.66, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, and 30 h). After a suitable washout period, each herb was given orally at doses of 25, 7.5, and 2.5 g, twice daily for 7 d. On the eighth day, theophylline was re-administrated orally and blood samples were collected. Plasma concentrations of theophylline were determined using HPLC and pharmacokinetic parameters were calculated using a non-compartmental analysis. Results: Treatment with fenugreek (25 g, orally) lead to a decrease in C-max and AUC(0-t) of theophylline of about 28% (p<0.05) and 22% (p<0.05), respectively, with no significant changes in T-1/2 lambda compared with the baseline values. Garden cress caused a decrease in C-max to a lesser extent and delayed T-max of theophylline (2.10 +/- 0.24 h versus 3.40 +/- 0.74 h), while AUC(0-infinity) increased by 37.44%. No significant effect was observed for the black seed treatment on theophylline disposition as measured by C-max, T-max, AUC(0-infinity), and CL/F. Discussion and conclusion: The concurrent use of fenugreek or garden cress alters theophylline pharmacokinetic behavior in an animal model. This could represent a modulation in cytochrome P450 activity, which is responsible for theophylline metabolism in beagle dogs. Further confirmation of these results in humans will warrant changes in theophylline dosing before the co-administration of such herbs.