Pharmacokinetic interaction of Acacia catechu with CYP1A substrate theophylline in rabbits

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• 作者：Abdullah Mohammed Al-Mohizea ; ^{abdulahad20@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Mohammad Raish ; Abdul Ahad ; ^{aahad@ksu.edu.sa" class="auth_mail" title="E-mail the corresponding author} ; Fahad Ibrahim Al-Jenoobi ; Mohd Aftab Alam
• 关键词：Acacia Catechu ; Cytochromes ; Herb-drug interactions ; Pharmacokinetics ; Theophylline
• 刊名：Journal of Traditional Chinese Medicine
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：35
• 期：5
• 页码：588-593
• 全文大小：467 K

文摘

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 Blood samples were withdrawn at different time intervals (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h) from the marginal ear vein.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 CYP1A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline, which may be due to inhibition of CYP1A.

Conclusion

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.