Kinetics of 1,2-dinitroglycerin following sustained release nitroglycerin: influence of propranolol and metoprolol.
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.
D000328:Adult; D001711:Biotransformation; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008790:Metoprolol / Q000494:pharmacology*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000097:blood*; D011433:Propranolol / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D011433:Propranolol; D005996:Nitroglycerin; D008790:Metoprolol