EFFECT OF THE SHORT-TERM ANCHUSAN TREATMENT ON CYP3A4-MEDIATED MIDAZOLAM METABOLISM IN HEALTHY SUBJECTS

DOI IR Web Site

Bibliographic Information

Other Title
  • 安中散短期投与のミダゾラム代謝に及ぼす影響
  • アンチュウサンタンキ トウヨ ノ ミダゾラム タイシャ ニ オヨボス エイキョウ

Search this article

Description

In Japan, many medical doctors utilize Kampo medicine in their daily practice in combination with Western medicine. However, there have been few reports investigating the drug-drug interactions via cytochrome P450 (CYP) between these medicines. In our previous study, long-term administration of anchusan increased the serum midazolam (MDZ) concentrations in rats and humans, suggesting the inhibition of intestinal CYP3A likely caused by the metabolites of anchusan constituents. To clarify the property of this effect, we conducted a short-term anchusan treatment study in human and investigated its effect on MDZ metabolism. The open-label, fixed-sequence, 2 period study was performed in 12 healthy men who were divided into two groups A and B. Each subject was administered 7.5mg MDZ orally as a control trial prior to the anchusan treatments. MDZ was administered again after either 2 hours (Group A) or 16 hours (Group B) of three times 2.5g anchusan treatments. Serial blood samples were collected over 8 hours after each MDZ dose. The serum MDZ concentrations were analyzed by HPLC and its pharmacokinetic parameters were determined. The visual analogue scale (VAS) was used for the estimation of the sedative effect. The short-term anchusan treatment did not show any remarkable change in MDZ pharmacokinetics (AUC0-8, Cmax and t1/2), although a statistically significant but minor decrease of AUC0-8 was observed after anchusan treatment in Group B. The VAS score showed a similar value between before and after anchusan treatment in both groups. The results showed that short-term (3 times) anchusan treatment did not inhibit MDZ pharmacokinetics and pharmacological effect, when MDZ was administered 2 or 16 hours after the last anchusan dose. CYP3A-mediated drug interaction caused by short-term anchusan does not occur under this condition.

Journal

Keywords

Details 詳細情報について

Report a problem

Back to top