Glyceryl-1-nitrate pharmacokinetics in healthy volunteers.

Abstract

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. 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. Mean intravenous clearance was 283 ml min-1 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. 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% (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. 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. 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.