title: Pharmacokinetic interaction of Acacia catechu with CYP1A substrate theophylline in rabbits.
abstract: OBJECTIVE
  To investigate the effect of black catechu (BC) on the pharmacokinetics of theophylline (CYP1A2 substrate, with narrow therapeutic index) in rabbits.
  
  
  METHODS
  In the present investigation the effect of BC on the pharmacokinetics of theophylline, a CYP1A2 substrate was determined. In the study, BC (264 mg/kg, p. o.) or saline (control group) was given to rabbits for 7 consecutive days and on the 8th day theophylline (16 mg/kg) was administered orally one hour after BC or saline treatment. Blood samples were withdrawn at different time intervals (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h) from the marginal ear vein.
  
  
  RESULTS
  The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration, time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%, 35.71% and 15.03%, respectively. While decreases in clearance, volume of distribution, and half-life were observed. It is suggested that BC pretreatment decreases the CYP1A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline, which may be due to inhibition of CYP1A.
  
  
  CONCLUSIONS
  BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1A and P-glycoprotein activity. Based on these results, precaution should be exercised when administering BC with CYP1A substrate.
authors.forename: Abdullah Mohammed
authors.initials: AM
authors.lastname: Al-Mohizea
authors.forename: Mohammad
authors.initials: M
authors.lastname: Raish
authors.forename: Abdul
authors.initials: A
authors.lastname: Ahad
authors.forename: Fahad Ibrahim
authors.initials: FI
authors.lastname: Al-Jenoobi
authors.forename: Mohd Aftab
authors.initials: MA
authors.lastname: Alam
mesh_terms: D000045:Acacia / Q000737:chemistry*; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011817:Rabbits; D013806:Theophylline / Q000493:pharmacokinetics*
chemical_list: D004365:Drugs, Chinese Herbal; D013806:Theophylline; D019363:Cytochrome P-450 CYP1A1