Biol Pharm Bull. 2002 Nov; 25(11): 1461-6.

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.

Ohnishi N, Okada K, Yoshioka M, Kuroda K, Nagasawa K, Takara K, Yokoyama T.

Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. ohnishi@mb.kyoto-phu.ac.jp

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.