title: Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs.
abstract: BACKGROUND
  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.
  
  
  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  Beagle dogs received theophylline (200 mg) orally and blood samples were withdrawn at different time intervals (0.33, 0.66, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, and 30 h).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 Cmax and AUC0-t of theophylline of about 28% (p < 0.05) and 22% (p < 0.05), respectively, with no significant changes in T1/2λ compared with the baseline values. Garden cress caused a decrease in Cmax to a lesser extent and delayed Tmax of theophylline (2.10 ± 0.24 h versus 3.40 ± 0.74 h), while AUC0-∞ increased by 37.44%. No significant effect was observed for the black seed treatment on theophylline disposition as measured by Cmax, Tmax, AUC0-∞, and CL/F.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutics and.
authors.forename: Fahad I
authors.initials: FI
authors.lastname: Al-Jenoobi
authors.forename: Abdul
authors.initials: A
authors.lastname: Ahad
authors.forename: Gamal M
authors.initials: GM
authors.lastname: Mahrous
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al-Mohizea
authors.forename: Khalid M
authors.initials: KM
authors.lastname: AlKharfy
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Al-Suwayeh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D041743:Herb-Drug Interactions; D031220:Lepidium sativum / Q000737:chemistry*; D008297:Male; D031881:Nigella sativa / Q000737:chemistry*; D028321:Plant Preparations / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*; D029910:Trigonella / Q000737:chemistry*
chemical_list: D028321:Plant Preparations; D013806:Theophylline
keywords: Cytochrome P450; disposition; herb–drug interaction