[Drug interaction of imipramine hydrochloride to the pharmacodynamics and pharmacokinetics of oxazepam].
In this report, we studied drug interaction between oxazepam and imipramine in rats. Oxazepam (20 mg/kg) and imipramine (20 or 50 mg/kg) were administrated orally. The oxazepam concentration in plasma, brain and liver were measured by the method of HPLC. The concomitant use of imipramine induced extension of the elimination half life (T 1/2 beta) and an increase of the area under the concentration time-curve (AUC) on the plasma concentration of oxazepam. With the concomitant use of imipramine, the AUC of oxazepam brain concentration increased approximately 1.42 to 1.56 in contradistinction to oxazepam alone. The anti-pentylenetetrazol effect of oxazepam at 1 hr after administration was increased by the concomitant use of imipramine, but there were no combination effects at 4 hr. The motor incoordination effect of oxazepam and diazepam was measured by the rotarod method. Oxazepam has little effect on the motor incoordination as compared with diazepam. The plasma protein binding of oxazepam was not changed by the combined use of imipramine both in vitro and in vivo. The pharmacodynamic effects of oxazepam were increased by the concomitant use of imipramine, and these effects were in reasonably good agreement with the change in brain concentration of oxazepam.
Department of Biochemical Pharmacology, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
M
M
Okiyama
K
K
Ueno
S
S
Ohmori
T
T
Igarashi
H
H
Kitagawa
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004347:Drug Interactions; D004357:Drug Synergism; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D010076:Oxazepam / Q000493:pharmacokinetics / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D001798:Blood Proteins; D010076:Oxazepam; D007099:Imipramine; D010433:Pentylenetetrazole