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Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine

A sensitive and simple chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to evaluate memantine in rat plasma. Memantine and propranolol (internal standard) in rat plasma was extracted using a methanol precipitation method. The standard curve value was 0.2–1000 ng/mL and selecti...

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Autores principales: Choi, Young A., Song, Im-Sook, Choi, Min-Koo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161283/
https://www.ncbi.nlm.nih.gov/pubmed/30082658
http://dx.doi.org/10.3390/pharmaceutics10030119
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author Choi, Young A.
Song, Im-Sook
Choi, Min-Koo
author_facet Choi, Young A.
Song, Im-Sook
Choi, Min-Koo
author_sort Choi, Young A.
collection PubMed
description A sensitive and simple chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to evaluate memantine in rat plasma. Memantine and propranolol (internal standard) in rat plasma was extracted using a methanol precipitation method. The standard curve value was 0.2–1000 ng/mL and selectivity, linearity, inter-day and intra-day accuracy and precision were within acceptance criteria. Using this validated method, drug-drug interactions between memantine and cimetidine was measured following co-administration of memantine and cimetidine intravenously and orally. Plasma exposure of memantine was increased by 1.6- and 3.0-fold by co-medication with cimetidine intravenously and orally, respectively. It suggested that the drug interaction occurred during the gut absorption process, which was consistent with the results showing that the intestinal permeability of memantine in the presence of cimetidine was 3.2-fold greater than that of memantine alone. Inhibition of cimetidine on hepatic elimination of memantine rather than renal excretion was also attributed to the drug-drug interaction between memantine and cimetidine, which explained the decreased clearance of memantine by co-medication with cimetidine. In conclusion, the newly developed simple and sensitive LC-MS/MS analytical method was applied to investigate the pharmacokinetic drug-drug interactions of memantine. Plasma exposure of memantine by co-administration with cimetidine was increased because of its enhanced intestinal permeability and the decreased metabolic activity of memantine.
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spelling pubmed-61612832018-10-01 Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine Choi, Young A. Song, Im-Sook Choi, Min-Koo Pharmaceutics Article A sensitive and simple chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to evaluate memantine in rat plasma. Memantine and propranolol (internal standard) in rat plasma was extracted using a methanol precipitation method. The standard curve value was 0.2–1000 ng/mL and selectivity, linearity, inter-day and intra-day accuracy and precision were within acceptance criteria. Using this validated method, drug-drug interactions between memantine and cimetidine was measured following co-administration of memantine and cimetidine intravenously and orally. Plasma exposure of memantine was increased by 1.6- and 3.0-fold by co-medication with cimetidine intravenously and orally, respectively. It suggested that the drug interaction occurred during the gut absorption process, which was consistent with the results showing that the intestinal permeability of memantine in the presence of cimetidine was 3.2-fold greater than that of memantine alone. Inhibition of cimetidine on hepatic elimination of memantine rather than renal excretion was also attributed to the drug-drug interaction between memantine and cimetidine, which explained the decreased clearance of memantine by co-medication with cimetidine. In conclusion, the newly developed simple and sensitive LC-MS/MS analytical method was applied to investigate the pharmacokinetic drug-drug interactions of memantine. Plasma exposure of memantine by co-administration with cimetidine was increased because of its enhanced intestinal permeability and the decreased metabolic activity of memantine. MDPI 2018-08-06 /pmc/articles/PMC6161283/ /pubmed/30082658 http://dx.doi.org/10.3390/pharmaceutics10030119 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Choi, Young A.
Song, Im-Sook
Choi, Min-Koo
Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine
title Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine
title_full Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine
title_fullStr Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine
title_full_unstemmed Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine
title_short Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine
title_sort pharmacokinetic drug-drug interaction and responsible mechanism between memantine and cimetidine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161283/
https://www.ncbi.nlm.nih.gov/pubmed/30082658
http://dx.doi.org/10.3390/pharmaceutics10030119
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