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

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).