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

Abstract

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 (T(max)), but did not influence the peak plasma concentration, area under the plasma concentration-time curve or terminal elimination half-life (t( 1/2 )). Each parameter for CBZ or CBZ-E with a single pretreatment with TJ-19 was not significantly different from that with the vehicle. T(max) and the elimination rate constant for CBZ were significantly increased by 1-week repeated pretreatment with T J-19, by 83% (p<0.01) and 88% (p<0.001), respectively. 1/2 and the mean residence time from zero to infinity (MRT(0-∞)) 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 μg/ml) was observed between the control and TJ-19 pretreatment groups. These results indicate that simultaneous oral administration of TJ19 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.