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.
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.
Ohnishi
Noriaki
N
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. ohnishi@mb.kyoto-phu.ac.jp
Okada
Kazuya
K
Yoshioka
Mutsunobu
M
Kuroda
Kazuo
K
Nagasawa
Kazuki
K
Takara
Koji
K
Yokoyama
Teruyoshi
T
D000818:Animals; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions / Q000502:physiology; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D041743:Herb-Drug Interactions; D029001:Herbal Medicine; D008519:Medicine, Traditional; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; C461320:shosaiko-to; D002220:Carbamazepine