Pharmacokinetics of glyceryl trinitrate and its main metabolites after application of glyceryl trinitrate tape (NT-1) in humans and dogs.

Abstract

A tape formulation (NT-1) containing glyceryl trinitrate (GTN) to increase its bioavailability and to avoid the first-pass effect in a liver was applied to the dog and the human, and then GTN, 1, 2-glyceryl dinitrate (GDN) and 1, 3-GDN in the blood was determined simultaneously by gas chromatography/negative ion chemical ionization-mass spectrometry (GC/NICI-MS). The blood concentration in dogs and human beings was as follows 1, 2-GDN>1, 3-GDN> GTN, and the absorption rate from the skin in the human beings was 10.8-12.2 times higher than that of the dog. The concentration of GTN in the dog reached a steady-state at 2 hours after the application of NT-1, and it was kept the level of 1 ng/ml of plasma until the final time of administration. After the exfoliation the blood concentration of GTN diminished rapidly. The concentration of GTN in human blood reached to a maximum level at 2 hrs after application of NT-1, and then it decreased slowly to 30-80 % of the maximum concentration following the exfoliation of the tape. After the exfoliation the blood level of GTN in human diminished rapidly to 1/2-1/5 of the concentration at the final time of administration. The blood pressure was related to the blood concentration of GTN, both in dogs and humans. This tape is highly safe and useful for the sustained release for a long time, and it is predicted to be effective to prevent an angina pectoris and to cure an acute cardiac failure.