Ohnishi Noriaki, Okada Kazuya, Yoshioka Mutsunobu, Kuroda Kazuo, Nagasawa Kazuki, Takara Koji, Yokoyama Teruyoshi
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
Biol Pharm Bull. 2002 Nov;25(11):1461-6. doi: 10.1248/bpb.25.1461.
The possibility of pharmacokinetic interactions between Sho-saiko-to extract powder (TJ-9), the most widely used traditional Chinese herbal (Kampo) medicine in Japan, and carbamazepine (CBZ), an important anti-epileptic drug, was examined in rats. There was no significant difference in the protein binding of CBZ in serum obtained before and after the single oral administration of TJ-9. The addition of TJ-9 to normal hepatic microsomes inhibited CBZ-10,11-epoxylase activity in a concentration-dependent manner. Liver weight, amounts of P450 and cytochrome b(5) in hepatic microsomes and the formation of carbamazepine-10,11-epoxide (CBZ-E), an active metabolite of CBZ, by microsomes were not influenced by 2-week repeated oral pretreatment with TJ-9 (1 g/kg/d), although pretreatments with phenobarbital (80 mg/kg/d, i.p.) significantly increased these parameters. The simultaneous oral administration of TJ-9 (1 g/kg) significantly decreased the peak plasma concentration of CBZ and the area under the concentration-time curve of CBZ-E, and lengthened the time to reach the peak concentration of CBZ after oral administration of CBZ. Two-week repeated oral pretreatment with TJ-9, however, did not affect the plasma concentration-time profile or any pharmacokinetic parameter of CBZ or CBZ-E. Also, a single oral administration of TJ-9 (1 g/kg) significantly delayed gastric emptying. These results indicated that the simultaneous oral administration of TJ-9 with CBZ to rats decreased the gastrointestinal absorption of CBZ, at least in part, by delaying gastric emptying, without affecting the metabolism of CBZ.
在大鼠中研究了日本使用最广泛的传统中药小柴胡汤提取物粉末（TJ - 9）与重要抗癫痫药物卡马西平（CBZ）之间药代动力学相互作用的可能性。单次口服TJ - 9前后获得的血清中CBZ的蛋白结合率无显著差异。向正常肝微粒体中添加TJ - 9以浓度依赖性方式抑制CBZ - 10,11 - 环氧化酶活性。肝微粒体中的肝重、P450和细胞色素b(5)的量以及CBZ的活性代谢物卡马西平 - 10,11 - 环氧化物（CBZ - E）的微粒体形成不受TJ - 9（1 g/kg/d）两周重复口服预处理的影响，尽管苯巴比妥（80 mg/kg/d，腹腔注射）预处理显著增加了这些参数。同时口服TJ - 9（1 g/kg）显著降低了CBZ的血浆峰值浓度和CBZ - E的浓度 - 时间曲线下面积，并延长了口服CBZ后达到CBZ峰值浓度的时间。然而，TJ - 9两周重复口服预处理并未影响CBZ或CBZ - E的血浆浓度 - 时间曲线或任何药代动力学参数。此外，单次口服TJ - 9（1 g/kg）显著延迟了胃排空。这些结果表明，TJ - 9与CBZ同时口服给大鼠至少部分地通过延迟胃排空降低了CBZ的胃肠道吸收，而不影响CBZ的代谢。
