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

Abstract

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Materials and methods: Beagle dogs received theophylline (200 mg) orally and blood samples were withdrawn at different time intervals (0.33, 0.66, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, and 30 h).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_1/2λ 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–∞ 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–∞, 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.

• Cytochrome P450
• disposition
• herb–drug interaction

Declaration of interest

The authors report no declarations of interest. This study was supported by the Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia (Grant number: DSR-AR-2-20).