Glyceryl trinitrate metabolism

Salvemini, D., Mollace, V., Pistelli, A., Anggard, E., Vane, J., Metabolism of glyceryl trinitrate to nitric oxide by endothelial cells and smooth muscle cells and its induction by E. coli lipopolysaccharide. Proc. Natl. Acad. Sci. USA 89 (1992), p. 982-986... 

Needleman, P., Harkey. A. B., Role of endogenous glutathione in the metabolism of glyceryl trinitrate by isolated perfused rat liver. Biochem. Pharmacol. 20 (1971), p. 1867-1876... 

Liu, Z., Brien, JF, Marks, GS, McLaughlin, BE, and Nakatsu, K. 1993. Lack of evidence for the involvement of cytochrome P-450 or other hemoproteins in metabolic activation of glyceryl trinitrate in rabbit aorta. J Pharmacol Exp Ther 264 1432-1439. 

Nitrates can be administered by various routes. For example, glyceryl trinitrate is used not only as traditional sublingual tablets but also in the form of modified-release tablets, buccal tablets, aerosolized oral spray, intravenous injection, and topical ointment or skin patches for percutaneous absorption (23). These different formulations have been developed largely as a means of controlling the onset and duration of action of glyceryl trinitrate, since in conventional oral form its action is limited by marked hepatic first-pass metabolism. 

Diltiazem is metabolized by CYP3A4 and was held responsible for unanticipated prolonged hypotension after sublingual glyceryl trinitrate in a patient who underwent coronary angiography 2 days after last using sildenafil (47). 

The drug may be inactivated in the liver on its way to the systemic circulation. An example of this is the inactivation of glyceryl trinitrate by hepatic monoxygenase enzymes during the first pass metabolism. 

Glyceryl trinitrate (GTN) is extremely effective at relieving the pain of angina but it has only a short half-life. Due to extensive first pass metabolism the drug is ineffective when taken orally and is administered sublingually or buccally in either tablet or aerosol form. 

IRrstnage metabolism AUorallyariminlstenddru passUvou the liver to the stemlc circulation. 5ome are so completely metabolized they am inactive orally - (e.g. Ildocafne, glyceryl trinitrate ... 

It was postulated that glyceryl trinitrate increased hepatic blood flow and therefore increased the metabolism of alteplase, which resulted in reduced plasma tPA levels. However, an in vitro study found that glyceryl trinitrate enhanced the degradation of alteplase, and therefore a mechanism other than increased hepatic blood flow seems likely to be involved. It has been suggested that this interaction may not be clinically important, and the current evidence is too sparse to warrant changing current practice. 

Glyceryl trinitrate was converted by rabbits to the mono-and 1,3-dinitrate derivatives, which were excreted in the urine. The isomeric 1,2-glyceryl dinitrate was not detected as a metabolite of glyceryl trinitrate. After the administration of 1,2-glyceryl dinitrate, only glyceryl mononitrate (isomeric position unknown) was detected. The metabolism of penta-erythritol trinitrate (IV), an active metabolite of pentaerythritol tetra-nitrate, was studied in dogs. The major metabolites in the urine were pentaerythritol mononitrate and pentaerythritol only the latter compound was present in the feces. An oral dose of pentaerythritol was excreted unchanged by the dog. ... 

Govoni, M., Casagrande, S., Maucci, R., Chiroli, V., and Tocchetti, P. (2006). In vitro metabolism of (Nitrooxy)butyl ester nitric oxide-releasing compounds Comparison with glyceryl trinitrate. J. Pharmacol. Exp. Ther. 317, 752-761. 

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