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Plasma concentrations of glyceryl trinitrate and its dinitrate metabolites after sublingual administration to volunteers. Simultaneous determination of glyceryl trinitrate and its dinitrate metabolites.

Arzneimittel-Forschung (1994-08-01)
K M Jensen, J B Dahl
ABSTRACT

The plasma profiles of nitroglycerin (glyceryl trinitrate, GTN, CAS 55-63-0) and its dinitrate metabolites (1,2-GDN and 1,3-GDN) were estimated after sublingual administration of GTN tablets 0.5 mg (Nitromex) given in single doses to 20 volunteers. Blood samples (totally 20) were collected to 2 h after administration, and the plasma concentrations of GTN, 1,2-GDN, and 1,3-GDN were measured simultaneously by gas chromatography. The pharmacokinetic parameters, Cmax, tmax, t1/2, and the dinitrate ratio (AUC1,2-GDN/AUC1,3-GDN) were determined for each subject. The plasma concentrations of GTN reached a maximum of 1.38 ng/ml (mean) (range: 0.32-3.18 ng/ml) after 4.9 min (mean) (range: 3-8 min). The plasma concentrations of 1,2-GDN and 1,3-GDN reached a maximum of 3.11 ng/ml (mean) (range: 1.14-5.44 ng/ml) and 0.70 ng/ml (mean) (range: 0.33-1.19 ng/ml) after 13.7 min (mean) (range: 8-40 min) and 17.6 min (mean) (range: 8-40 min). The t1/2 values (mean) were 3.3, 35.5, and 38.1 min for GTN, 1,2-GDN, and 1,3-GDN, respectively. The dinitrate ratio was estimated to be 4.1 (mean).

MATERIALS
Product Number
Brand
Product Description

Supelco
1,3-Dinitroglycerin solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
1,3-Dinitroglycerin solution, 100 μg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®