A Study of Digoxin Concentrations in the Mouse Brain after Chronic Treatment with Escitalopram

Asari Shohei, Osada Kenichi, Watanabe Takashi, Haga Toshiaki, Kocha Hiroki

doi:10.14963/stmari.44.221

<p>P-glycoprotein (P-gp) is a membrane protein present in the brain, liver, and kidney that has a major role in drug delivery. Escitalopram, a selective serotonin reuptake inhibitor, is transported as a substrate of P-gp. Digoxin, which is also a known substrate of P-gp, is used to evaluate the drug delivery function of P-gp.<br/>Because previous investigations of P-gp have been mainly short-term studies, we examined the effect of the chronic administration of antidepressants on the function of P-gp. We administered oral escitalopram 10 mg/kg/day to C57BL/6 mice for 6 weeks. Digoxin 2 mg/kg was then administered intraperitoneally 2 hours before dissection. We examined the activation effect of P-gp on ATPase using a luciferase luminescent reaction. The P-gp activity in the mice that received a combination of escitalopram and verapamil showed an additive effect, whereas those receiving a combination of escitalopram and digoxin displayed a synergistic increase in P-gp activity. The concentration of digoxin in the brain significantly increased from 0.7125 ng/g at week 0 to 1.158 ng/g at week 6. We believe we are the first to report this synergistic effect between escitalopram and digoxin on the P-gp activity on ATPase. We hypothesize that chronic treatment with escitalopram inhibited the excretion of digoxin from the brain through P-gp, causing the concentration of digoxin to increase.<br/>In conclusion, we observed an increase in digoxin concentration in the mouse brain mediated by the drug-drug interaction of escitalopram and digoxin.</p>

A Study of Digoxin Concentrations in the Mouse Brain after Chronic Treatment with Escitalopram

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