Effects of subacutely administered saiboku-to, an oriental herbal medicine, on pharmacodynamics and pharmacokinetics of diazepam in rodents.
Subacute treatment with saiboku-to (2000 mg/kg, p.o., once a day) for 7 days induced an anxiolytic-like effect in rats. It did not, however, produce any other effects, such as sedative and hypnotic effects, anticonvulsive and muscle relaxant effects except for anxiolytic effect observed in diazepam-injected rats or mice. Diazepam (1.0 mg/kg, s.c.) induced anxiolytic-like effect was enhanced in saiboku-to treated rats as an additional effect of that induced by saiboku-to. To elucidate whether the enhancement of the anxiolytic-like effect following combined administration of diazepam and saiboku-to is due to the inhibition of hepatic drug-metabolizing enzymes, the pharmacokinetics of diazepam were further investigated in saiboku-to treated rats. The pharmacokinetic studies clearly demonstrated that subacute treatment with saiboku-to did not affect plasma concentration and protein binding rate of diazepam, and the activities of hepatic drug-metabolizing enzymes related to diazepam metabolism. These results, taken together, suggest that the enhancement of diazepam-induced anxiolytic-like effect observed in saiboku-to-treated rats is not due to an inhibition of diazepam metabolism.
Yuzurihara
M
M
Kampo & Pharmacognosy Laboratories, Tsumura, Ibaraki, Japan.
Ikarashi
Y
Y
Ishihara
K
K
Kushida
H
H
Ishige
A
A
Sasaki
H
H
Maruyama
Y
Y
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D003975:Diazepam / Q000493:pharmacokinetics / Q000494:pharmacology*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D014151:Anti-Anxiety Agents; D004365:Drugs, Chinese Herbal; D011963:Receptors, GABA-A; C045086:saiboku-to; D003577:Cytochrome P-450 Enzyme System; D003975:Diazepam; D002118:Calcium