Kinetics of 1,2-dinitroglycerin following sustained release nitroglycerin: influence of propranolol and metoprolol

• Published in: Klinische Wochenschrift 1985-11, Vol.63 (22), p.1170-1173
• Main Authors: Ochs, H R, Verburg-Ochs, B, Greenblatt, D J
• Format: Article
• Language: English
• Subjects: Adult; Biotransformation; Delayed-Action Preparations; Drug Interactions; Humans; Kinetics; Metabolic Clearance Rate - drug effects; Metoprolol - pharmacology; Nitroglycerin - administration & dosage; Nitroglycerin - blood; Propranolol - pharmacology
• ISSN: 0023-2173; 1432-1440
• DOI: 10.1007/BF01740593

Ten healthy volunteers ingested a single 18-mg oral dose of sustained release nitroglycerin (TNG) (Giulini-Pharma) on three occasions: once in the control state, once during coadministration of propranolol (80-mg three times daily), and once during coadministration of metoprolol (100-mg twice daily). The degree of beta adrenergic blockade was evaluated by the metaproterenol infusion test. Plasma concentration of TNG and its major metabolite, 1,2-dinitroglycerin (DNG), during 12 h after each dose were measured by gas chromatography-mass spectrometry. Intact TNG was not detected in the plasma of any patient. The major metabolite, DNG, was easily measurable in blood, and had a biphasic plasma concentration profile. Coadministration of the beta-blockers had no influence on any of the kinetic variables for DNG. The mean values during control, propranolol, and metoprolol trials of DNG elimination half-life were: 1.35, 1.10, and 1.09 h; total area under the curve: 42, 38, and 42 ng/ml X h; oral clearance: 6.6, 7.2, and 6.4 liters/min. Thus TNG when administered as a sustained release oral preparation is rapidly and completely transformed to DNG. There was no pharmacokinetic interaction between sustained release TNG and two commonly used beta-blocking agents, suggesting that any clinical interaction that may-occur between sustained release nitroglycerin and beta-blocking agents is pharmacodynamic rather than pharmacokinetic in nature.