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标题：Studies on Interactions between Traditional Herbal and Western Medicines. V. Effects of Sho-saiko-to (Xiao-Cai-hu-Tang) on the Pharmacokinetics of Carbamazepine in Rats
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作者：Noriaki Ohnishi ; Kazuya Okada ; Mutsunobu Yoshioka 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：11
页码：1461-1466
DOI：10.1248/bpb.25.1461
出版社：The Pharmaceutical Society of Japan
摘要：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 b₅ 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.
关键词：Sho-saiko-to (TJ-9);carbamazepine;pharmacokinetic interaction;P450;gastric emptying;rat