Studies on interactions between traditional herbal and Western medicines. IV: lack of pharmacokinetic interactions between Saiko-ka-ryukotsu-borei-to and carbamazepine in rats.

摘要

The possibility of pharmacokinetic interactions between Saiko-ka-ryukotsu-borei-to extract powder (TJ-12), a widely used traditional Chinese herbal (Kampo) medicine, and carbamazepine (CBZ), an important anti-epileptic drug, was examined in rats. There were no significant differences in the serum protein binding of CBZ and carbamazepine- 10,11-epoxide (CBZ-E), its active metabolite, at two concentrations (1 and 10 Bg/ml) between twogroups pretreated orally with the vehicle andTJ-12 suspension (1 g/kg/d, p.o.) for 1 week. One-week repeated pretreatment with TJ- 12 (1 g/kg/d) did not influence liver weight, contents of cytochromes P450 and b5 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 parameters. Neither a single nor 1-week repeated oral pretreatment with TJ-12 (1 g/kg/d) affected the plasma concentration-time profile and any pharmacokinetic 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 no effect ofthe pharmacokinetics of CBZ or CBZ-E in rats. Concomitant treatment with TJ- 12 and CBZ appears to be pharmacokinetically safe in humans.