Studies on interactions between traditional herbal and Western medicines. IV: lack of pharmacokinetic interactions between Saiko-ka-ryukotsu-borei-to and carbamazepine in rats.
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.
Ohnishi
N
N
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Japan.
Nakasako
S
S
Okada
K
K
Umehara
S
S
Takara
K
K
Nagasawa
K
K
Yoshioka
M
M
Kuroda
K
K
Yokoyama
T
T
D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D002220:Carbamazepine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D041743:Herb-Drug Interactions; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D020835:Medicine, Kampo; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D001798:Blood Proteins; D004365:Drugs, Chinese Herbal; C095444:saiko-ka-ryukotsu-borei-to; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System