Application of high-performance liquid chromatography with synchronized accumulating radioisotope detector to analysis of glyceryl trinitrate and its metabolites in rat plasma

Baba, Shigeo; Shinohara, Yoshihiko; Sano, Hiroshi; Inoue, Tsuneaki; Masuda, Sachiko; Kurono, Masayasu

doi:10.1016/s0378-4347(00)83319-8

Cited by 10 publications

(1 citation statement)

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“…Glyceryl-1-nitrate (G-1-N) was found to be an intermediate metabolic product in the stepwise de-esterification of glyceryl trinitrate in animals and humans (Baba et al, 1984;Bogaert et al, 1971;Hodgson et al, 1977;Laufen et al, 1986a;Laufen & Leitold, 1986;Short et al, 1977;Spanggord et al, 1980), which is schematically represented by Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Glyceryl‐1‐nitrate pharmacokinetics in healthy volunteers.

Laufen

Leitold

1987

Brit J Clinical Pharma

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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.

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Section: Introductionmentioning

confidence: 99%

Glyceryl‐1‐nitrate pharmacokinetics in healthy volunteers.

Laufen

Leitold

1987

Brit J Clinical Pharma

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Pharmacokinetics of oral glycerol-1-nitrate

Laufen¹,

Leitold²,

Yeates³

1986

Eur J Clin Pharmacol

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The plasma kinetics and urinary excretion of glycerol-1-nitrate (G-1-N), a water soluble metabolite of glycerol trinitrate with anti-anginal potential, have been investigated in healthy human volunteers following oral doses of 10, 20 and 40 mg tablets and 20 mg as drops. In all volunteers G-1-N was rapidly absorbed. The mean concentration-time curves peaked 40 min after administration of tablets at 144 ng/ml (10 mg), 308 ng/ml (20 mg) and 573 ng/ml (40 mg). After the drops the peak of 324 ng/ml occurred at 1 h. The areas under the G-1-N concentration-time curve and the G-1-N peak heights were linear with dose. Tablets and drops can be regarded as bioequivalent with respect to area under the curve and elimination half-life. The bioavailability of the 20 mg tablet relative to the 20 mg drops was 98.6% in terms of area under the curve. The mean apparent half-life of G-1-N elimination from plasma was 2.69 +/- 0.67 h (n = 46). The mean residence time of G-1-N in the body was 4.65 h compared to 0.28 h for glycerol trinitrate after buccal administration. Female volunteers were found to have significantly lower areas under the curve than male volunteers. The difference was probably due to differences in body weight. Renal excretion does not play an important role in the elimination of oral G-1-N from the body. An overall average of 5.42% of the G-1-N dose was excreted in the urine; free drug accounted for 4.02% and conjugated drug for 1.40%.

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