Pharmacokinetic interaction of Acacia catechu with CYP1A substrate theophylline in rabbits

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the 8^(th)day theophylline(16 mg/kg) was administered orally one hour after BC or saline treatment.Blood samples were withdrawn at different time intervals(0.5,1,1.5,2,3,4,6,8,12,24 and 36 h) from the marginal ear vein.RESULTS:The pretreatment of rabbits with BC resulted in a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 CYP1 A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline,which may be due to inhibition of CYP1 A.CONCLUSION:BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1 A and P-glycoprotein activity.Based on these results,precaution should be exercised when administering BC with CYP1 A substrate.