Studies on interactions between traditional herbal and western medicines. IV: Lack of pharmacokinetic interactions between Saiko-ka-ryukotsu-borei-toand carbamazepine in rats

The possibility of pharmacokinetic interactions between Saiko-ka-ryukotsu-b orei-to extract powder (TJ-12), a widely used traditional Chinese herbal (K ampo) medicine, and carbamazepine (CBZ), an important anti-epileptic drug, was examined in rats. There were no significant differences in the serum pr otein binding of CBZ and carbamazepine-10,11-epoxide (CBZ-E), its active me tabolite, at two concentrations (1 and 10 Bg/ml) between two groups pretrea ted orally with the vehicle and TJ-12 suspension (1 g/kg/d, p.o.) for 1 wee k. One-week repeated pretreatment with TJ-12 (I g/kg/d) did not influence l iver weight, contents of cytochromes P450 and b(5) in hepatic microsomes or the formation rate of CBZ-E from CBZ by its microsomes, while pretreatment with phenobarbital (80 mg/kg/d, i.p.) significantly increased these parame ters. Neither a single nor 1-week repeated oral pretreatment with TJ-12 (1 g/kg/d) affected the plasma concentration-time profile and any pharmacokine tic parameter of CBZ or CBZ-E after oral administration of CBZ (50 mg/kg). These results indicated that oral co-administration of TJ-12 with CBZ has n o effect of the pharmacokinetics of CBZ or CBZ-E in rats. Concomitant treat ment with TJ-12 and CBZ appears to be pharmacokinetically safe in humans.