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

The effects of oral co- and pre-administration of Sho-seiryu-to extract pow der (TJ-19, 1 g/kg), a widely used Kampo (traditional Chinese herbal) medic ine, 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 simultane ous administration of TJ-19 significantly lengthened the time to reach the peak plasma concentration (T-max), but did not influence the peak plasma co ncentration, area under the plasma concentration-time curve or terminal eli mination 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 TJ-19, by 83% (p<0.01) and 88% (p<0.001), respectively, t(1/2) and the mean residence time from zero t o infinity (MRT0-x) in the TJ-19 pretreatment group were significantly shor tened, by 52 and 34% (p<0.005), respectively. No significant difference in the bound fraction of each drug at two concentrations (1 and 10 mu g/ml) wa s observed between the control and TJ-19 pretreatment groups. These results indicate that simultaneous oral administration of TJ-19 delays the oral ab sorption of CBZ, while 1-week repeated pretreatment with TJ-19 accelerates the metabolism of CBZ in rats, without affecting the protein binding of CBZ .