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- W2024595280 abstract "The pharmacokinetic and pharmacodynamic aspects of organic nitrates are discussed, with particular emphasis on the 3 major organic nitrates currently in use, nitroglycerin (NTG), isosorbide dinitrate and isosorbide-5-mononitrate. After intravenous administration, both NTG and isosorbide dinitrate exhibit large systemic clearances and both nitrates appear to be extensively distributed in vascular and other peripheral tissues. Two pharmacokinetic features appear particularly notable for NTG: there is a significant arteriovenous extraction of the drug, and its systemic clearance is related to cardiac output. Both of these features, plus other evidence, suggest that organic nitrates may be substantially removed from the systemic circulation by the vasculature itself. During nitrate tolerance, plasma drug concentrations remain elevated, but vascular activity is diminished. This apparent paradox might be explainable by a unifying hypothesis of reduced nitrate metabolism during vascular tolerance; thus, in the tolerant state, reduced systemic clearance of the intact drug brought about elevated plasma concentrations, whereas reduced cellular metabolism at the smooth muscle brought about a decrease in vascular activity. The complex relations among plasma kinetics, vascular metabolism and pharmacologic action of organic nitrates are still poorly understood." @default.
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- W2024595280 date "1987-11-01" @default.
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- W2024595280 title "Pharmacokinetics and pharmacodynamics of organic nitrates" @default.
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- W2024595280 doi "https://doi.org/10.1016/0002-9149(87)90543-1" @default.
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