A sensitive and simple chromatography-tandem mass spectrometry (LC-MS/MS) method\nwas developed to evaluate memantine in rat plasma. Memantine and propranolol (internal standard)\nin rat plasma was extracted using a methanol precipitation method. The standard curve value was\n0.2â??1000 ng/mL and selectivity, linearity, inter-day and intra-day accuracy and precision were within\nacceptance criteria. Using this validated method, drug-drug interactions between memantine and\ncimetidine was measured following co-administration of memantine and cimetidine intravenously\nand orally. Plasma exposure of memantine was increased by 1.6- and 3.0-fold by co-medication\nwith cimetidine intravenously and orally, respectively. It suggested that the drug interaction\noccurred during the gut absorption process, which was consistent with the results showing that the\nintestinal permeability of memantine in the presence of cimetidine was 3.2-fold greater than that of\nmemantine alone. Inhibition of cimetidine on hepatic elimination of memantine rather than renal\nexcretion was also attributed to the drug-drug interaction between memantine and cimetidine, which\nexplained the decreased clearance of memantine by co-medication with cimetidine. In conclusion,\nthe newly developed simple and sensitive LC-MS/MS analytical method was applied to investigate\nthe pharmacokinetic drug-drug interactions of memantine. Plasma exposure of memantine by\nco-administration with cimetidine was increased because of its enhanced intestinal permeability and\nthe decreased metabolic activity of memantine.
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