A Study of Digoxin Concentrations in the Mouse Brain after Chronic Treatment with Escitalopram
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- Asari Shohei
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Osada Kenichi
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Watanabe Takashi
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Haga Toshiaki
- Department of Neuropsychiatry, St. Marianna University School of Medicine
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- Kocha Hiroki
- Department of Neuropsychiatry, St. Marianna University School of Medicine
Bibliographic Information
- Other Title
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- エスシタロプラム長期投与による脳内ジゴキシン濃度の検討
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Description
<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>
Journal
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- The St. Marianna Medical Journal
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The St. Marianna Medical Journal 44 (4), 221-229, 2017
St. Marianna University Society of Medical Science
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Details 詳細情報について
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- CRID
- 1390001204963620992
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- NII Article ID
- 130005494212
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- ISSN
- 21890285
- 03872289
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- Text Lang
- ja
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- Data Source
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- JaLC
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed