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Pharmacokinetics of organic nitrates in man: an overview.

The pharmacokinetics of glyceryl trinitrate are still not completely understood. The substance disappears rapidly from plasma largely by extrahepatic mechanisms. It is converted in glyceryl dinitrates and glyceryl mononitrates. After transdermal application of a controlled delivery system, plasma concentrations of glyceryl trinitrate can be maintained over the time period of application but, as for other routes, there are important intra- and inter-individual variations and fluctuations. Isosorbide dinitrate disappears less rapidly from the body; it is converted to the isosorbide mononitrates. Plasma concentrations of isosorbide dinitrate and mononitrates are quite predictable in different circumstances, e.g. on application of oral sustained release formulations. Measurement of the plasma concentrations of nitrates has been used to characterize different preparations and routes of administration. However, these plasma concentrations cannot be used to predict the effect, probably because of the important counter-regulation and tolerance which develop rapidly after administration of the drugs.