Kinetic Analysis on Decomposition of Pentaerythrityl Tetranitrate under Influence of Thiols

Abstract

Pentaerythrityl tetranitrate (PETN) is an organic nitrate compound used in the therapy as
general vasodilator in the treatment of angina pectoris. PETN acts as prodrug for nitric oxide
as active component. However, in clinical association, it is known a decreased ability of
organic nitrate to do chemical reduction, which is metabolic tolerance, by upregulation in
endogenic thiol system. It has been proved that supplementation of thiol is able to overcome
tolerance to nitrate, nevertheless there is no comprehensive reports on interaction between
organic nitrate and thiol compounds. The goal of this research is to study decomposition
reaction kinetic of PETN under influence N-acetyl cysteine (NAC) and thiosalicylic acid
(TSA) as thiol compounds, in the physiological condition. PETN as tracing compound were
monitored by chromatographic system, with ratio of thiols used was equal, doubled, five
times, and ten times folds. Data were analyzed kinetically by using math equation for reaction
order 1, 2, and composite order 1 (equivalence). The result showed the linearity values on
kinetic derivative, where correlation coefficient, r, is higher than 0.9 (r ≥ 0.9) for composite
order 1. The result will give scientific contribution about tolerance phenomena in organic
nitrate, particularly in the role of thiol compound to overcome nitrate tolerance.