Pharmacokinetic and pharmacodynamic studies of drug interaction following oral administration of imipramine and sodium alginate in rats

摘要

Recently, the use of health foods has increased due to growing interest in health maintenance. Previous in vitro studies have shown some drugs to be adsorbed by sodium alginate, a dietary fiber, and that such adsorption was marked with tricyclic antidepressants, such as imipramine. This study investigated the pharmacokinetic and pharmacological interactions between imipramine and sodium alginate in rats. The simultaneous administration of imipramine (30 mg/kg, oral (p.o.)) and sodium alginate (3.0%, p.o.) decreased the antidepressant-like activity of imipramine in a forced swimming test. In the rats administrated imipramine and 0.3%, 1.0%, or 3.0% sodium alginate, the geometric mean ratio of the C _max values of imipramine was 72% [90% confidence intervals (CI) = 53–91%], 64% (90% CI = 47–80%), and 58% (90% CI = 50–67%), respectively. The geometric mean ratio of the AUC_0–6 values of imipramine were 68% (90% CI = 56–80%), 74% (90% CI = 60–89%), and 87% (90% CI = 73–102%), respectively. The decrease in C _max and AUC_0–6 was judged to be significant with a 90% CI outside the 80–125% boundaries. In addition, the T _max value of imipramine significantly increased (P < 0.05) by coadministration with 3.0% sodium alginate. These results suggested that simultaneous administration of sodium alginate decreased the serum concentration and pharmacological action of imipramine, through a delay in its absorption. Although the clinical relevance of these findings is unclear, it is important to pay considerable attention to the interactions between imipramine and sodium alginate.