Peng Wen-Xing, Li Huan-De, Zhou Hong-Hao
Department of Clinical Pharmacy of the Second Xiangya Hospital, Central South University, Changsha, China.
Eur J Clin Pharmacol. 2003 Jul;59(3):237-41. doi: 10.1007/s00228-003-0596-0. Epub 2003 May 17.
To examine the potential effect of daidzein on CYP1A2 activity and on the pharmacokinetics of theophylline by inhibiting its metabolism.
The experiment was conducted in a single-blind, placebo-controlled, parallel study. The caffeine metabolic ratio (CMR) used as an indicator of CYP1A2 function was completed at baseline and after daidzein or placebo co-administration. A single dose of 100 mg theophylline was taken by all 20 volunteers on day 3. Thereafter, volunteers were allocated for one of two regimens. One group received 200 mg daidzein twice daily for 10 days. The other group received placebo. On day 12, the test group received 200 mg daidzein with 100 mg theophylline; the parallel group received 100 mg theophylline with placebo.
The baseline value of CMR between test group and control group did not show a difference (P=0.215). The percentage decrease in CMR ranged from -50% to 20%, with an average value of -19.8+/-19.7%. The percentage decrease in test group was statistically significant (P=0.009), and no significant changes were shown in the control group (t=0.12, P=0.914). By comparing the pharmacokinetic parameters of theophylline before and after daily treatment with daidzein, the effect of daidzein on the metabolism of theophylline was evident. Comparing the kinetics parameters of theophylline of day 1 (without co-medication) with those of day 12 (10-day daidzein), the AUC(0-48), AUC(0- infinity ), C(max) and t(1/2) were significantly increased by 33.57+/-21.75% (CI, 1.21-1.46, P< 0.05), 33.77+/-21.45% (CI, 1.20-1.46, P<0.05), 23.54+/-16.93% (CI, 1.23-1.52, P< 0.05) and 41.39+/-45.92% (t=-3.19, P=0.011), respectively. The pharmacokinetic parameters of theophylline within the placebo group showed no statistically significant difference (P >0.05).
Daidzein, a principal isoflavone in soybean, in higher doses may inhibit CYP1A2 activity in vivo, and physicians should be aware of potential drug-food interactions.
通过抑制茶碱代谢来研究大豆苷元对CYP1A2活性及茶碱药代动力学的潜在影响。
实验采用单盲、安慰剂对照、平行研究。以咖啡因代谢率（CMR）作为CYP1A2功能指标，在基线期以及大豆苷元或安慰剂共同给药后进行测定。20名志愿者在第3天均服用100mg单剂量的茶碱。此后，志愿者被分配至两种治疗方案之一。一组每日两次服用200mg大豆苷元，共10天。另一组服用安慰剂。在第12天，试验组服用200mg大豆苷元与100mg茶碱；平行组服用100mg茶碱与安慰剂。
试验组与对照组的CMR基线值无差异（P = 0.215）。CMR降低百分比范围为-50%至20%，平均值为-19.8±19.7%。试验组的降低百分比具有统计学意义（P = 0.009），而对照组未显示出显著变化（t = 0.12，P = 0.914）。通过比较每日用大豆苷元治疗前后茶碱的药代动力学参数，大豆苷元对茶碱代谢的影响明显。比较第1天（未联合用药）与第12天（10天大豆苷元治疗）的茶碱动力学参数，AUC(0 - 48)、AUC(0 - ∞)、C(max)和t(1/2)分别显著增加33.57±21.75%（CI，l.21 - 1.46，P < 0.05）、33.77±21.45%（CI，1.20 - 1.46, P < 0.05）、23.54±16.93%（CI，1.23 - 1.52，P < 0.05）和41.39±45.92%（t = -3.19，P = 0.011）。安慰剂组内茶碱的药代动力学参数无统计学显著差异（P > 0.05）。
大豆中的主要异黄酮大豆苷元，高剂量时可能在体内抑制CYP1A2活性,医生应注意潜在的药物 - 食物相互作用。
