PMID: 2498508Apr 1, 1989Paper

Kinetic mechanisms for the concentration dependency of in vitro degradation of nitroglycerin and glyceryl dinitrates in human blood: metabolite inhibition or cosubstrate depletion?

Journal of Pharmaceutical Sciences
S Chong, H L Fung

Abstract

The in vitro degradation of nitroglycerin (NTG) and its dinitrate metabolites in human blood and red blood cells (RBC) has been shown to exhibit apparent first-order kinetics. The decay rates of NTG and its dinitrate metabolites, however, were dependent on the initial concentration. We showed that this unusual kinetic behavior can be described mathematically by models of Michaelis-Menten kinetics combined with either competitive product inhibition or cosubstrate depletion. Experimental studies were conducted to determine the relative contribution of these two mechanisms to the observed kinetics. The effect of added thiols (the likely cosubstrates) on [14C]NTG degradation was studied separately in whole blood, reconstituted RBC, lysed RBC, and plasma. N-Acetylcysteine, L-cysteine, and D-cysteine accelerated NTG degradation in whole blood, while a similar concentration of glutathione had no effect. However, all four thiols exerted no effect on NTG kinetics in reconstituted and lysed RBC. In contrast, these thiols, as well as dithiothreitol, produced a marked increase (3-14 fold) in NTG degradation rate in plasma compared with buffer controls. Since thiol replenishment in reconstituted and lysed RBC did not abolish the concentrati...Continue Reading

References

Dec 1, 1970·Clinica Chimica Acta; International Journal of Clinical Chemistry·E HegeshH I Shuval

❮ Previous
Next ❯

Citations

Oct 1, 1994·Cardiovascular Drugs and Therapy·K E Torfgård, J Ahlner
Nov 1, 1993·British Journal of Pharmacology·D SalveminiE Anggard
Feb 19, 2009·The Journal of Pharmacology and Experimental Therapeutics·Pei-Suen TsouHo-Leung Fung
Feb 27, 2003·Clinical Pharmacokinetics·Satoru Hashimoto, Atsuko Kobayashi
Feb 26, 2016·Antioxidants & Redox Signaling·Annie Beuve
Sep 3, 2009·Pharmacology & Therapeutics·Rebecca H RitchieBarbara K Kemp-Harper

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.