Biol Pharm Bull. 1999 May; 22(5): 527-31.

Studies on interactions between traditional herbal and Western medicines. I. Effects of Sho-seiryu-to on the pharmacokinetics of carbamazepine in rats.

Ohnishi N, Yonekawa Y, Nakasako S, Nagasawa K, Yokoyama T, Yoshioka M, Kuroda K.

Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Japan.

The effects of oral co- and pre-administration of Sho-seiryu-to extract powder (TJ-19, 1 g/kg), a widely used Kampo (traditional Chinese herbal) medicine, on the pharmacokinetics of an anti-epileptic drug, carbamazepine (CBZ), and its active metabolite (carbamazepine-10,11-epoxide, CBZ-E) after oral administration of CBZ (50 mg/kg) were examined in male rats. The simultaneous administration of TJ-19 significantly lengthened the time to reach the peak plasma concentration (Tmax), but did not influence the peak plasma concentration, area under the plasma concentration-time curve or terminal elimination half-life (t1/2). Each parameter for CBZ or CBZ-E with a single pretreatment with TJ-19 was not significantly different from that with the vehicle. Tmax and the elimination rate constant for CBZ were significantly increased by 1-week repeated pretreatment with TJ-19, by 83% (p<0.01) and 88% (p<0.001), respectively. t1/2 and the mean residence time from zero to infinity (MRT0-infinity) in the TJ-19 pretreatment group were significantly shortened, by 52 and 34% (p<0.005), respectively. No significant difference in the bound fraction of each drug at two concentrations (1 and 10 microg/ml) was observed between the control and TJ-19 pretreatment groups. These results indicate that simultaneous oral administration of TJ-19 delays the oral absorption of CBZ, while 1-week repeated pretreatment with TJ-19 accelerates the metabolism of CBZ in rats, without affecting the protein binding of CBZ.