Glyceryl‐1‐nitrate pharmacokinetics in healthy volunteers.

Abstract

1 The plasma kinetics and urinary excretion of glyceryl-1-nitrate (G-1-N), a metabolite of glyceryl trinitrate with antianginal potential, were investigated in 10 healthy male volunteers, after intravenous infusion and oral administration of 20 mg G-1-N. 2 The apparent volume of G-1-N distribution was 601 corresponding to 0.761 kg-1 body weight, on average. It is suggested that total body water is the principal biological correlate of the hydrophilic drug.3 Mean intravenous clearance was 283 ml min-' or 3.61 ml min-1 kg-1. The average of elimination half-lives were 2.50 ± 0.36 (s.d.) h after the intravenous and 2.54 ± 0.40 (s.d.) h after the oral dose. 4 Inter-subject variances of pharmacokinetic parameters were low compared to variances reported for glyceryl trinitrate. The coefficient of intra-subject variation of the elimination half-lives was 8.8%. 5 5.5% (i.v.) and 5.4% (p.o.) of the administered dose were excreted into urine up to 48 h after the administration. 1% (i.v.) and 1.5% (p.o.) were in the conjugated form. 6 The oral dose was rapidly and almost completely absorbed. The oral bioavailability on the basis of areas under the curve amounted to 88.6% on the average. 7 For clinical use, owing to its high oral bioavailability, long residence in the body, inactivation by metabolic conversion, and good predictability of kinetic parameters, G-1-N offers advantage over glyceryl trinitrate.

Nitroglycerin [BAT Value Documentation, 1998]

“…After oral and intravenous administration of 1-glycerol mononitrate, plasma concentrations of up to 300 ng/ml were found (56). Bioavailability after ingestion is on average 89 %.…”

“…Five percent is bound to plasma proteins and is excreted with the urine in man as a product of nitroglycerin metabolism (56). The pharmacokinetics and excretion of 1-glycerol mononitrate were investigated in 10 healthy volunteers after intravenous and oral administration of 20 mg 1-glycerol mononitrate (56).…”

“…Biotransformation of nitroglycerin takes place in the intestinal mucous membrane, in the liver and kidneys, in smooth endothelial and muscle cells of the vessels and in erythrocytes (6,24,56,72). Metabolism of nitroglycerin takes place via denitration mechanisms, very probably with glutathione.…”

Nitroglycerin for treatment of retained placenta: A randomised, placebo-controlled, multicentre, double-blind trial in the UK

“…Nitroglycerin can be administered either sublingually or intravenously. Both routes of administration have the same pharmacokinetic properties, with the onset of action within 2 to 3 minutes and peak plasma concentrations approximately 6 to 7 minutes post‐dose [32]. We chose to use sublingual spray because, compared to sublingual tablets, the spray has several advantages including significant reduction in latency of onset, fewer objective and subjective side effects, and stability at room temperature [33].…”