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Interaction of nitroglycerin with human blood components
Journal of Pharmaceutical Sciences
|April 1, 1983
Summary
Nitroglycerin rapidly disappears from blood, but the loss may be physical, not enzymatic. Its disappearance rate depends on concentration, suggesting a mixed kinetic mechanism requiring further study for drug analysis.
Area of Science:
- Pharmacology
- Biochemistry
- Physical Chemistry
Background:
- Nitroglycerin is known to be rapidly lost from blood solutions.
- Previous assumptions suggested enzymatic degradation as the primary cause of nitroglycerin loss.
Purpose of the Study:
- To investigate the mechanism of nitroglycerin disappearance in red blood cells and whole blood.
- To determine if the loss is enzymatic, chemical, or physical.
Main Methods:
- Incubation of nitroglycerin with washed red blood cells at 37 degrees Celsius.
- Analysis of nitroglycerin disappearance kinetics across a concentration range of 10-480 ng/ml.
- Comparison of nitroglycerin and its metabolites' reaction rates.
Main Results:
- Nitroglycerin loss exhibits an initial rapid phase followed by a concentration-dependent first-order process.
- Half-life increases with initial concentration (4 min at 10 ng/ml to 52 min at 480 ng/ml), indicating a mixed kinetic mechanism.
- Metabolites (dinitroglycerins) show similar kinetics but react significantly slower.
Conclusions:
- The rapid loss of nitroglycerin from blood may involve a physical mechanism rather than solely enzymatic degradation.
- The concentration-dependent kinetics suggest a complex interaction with red blood cells.
- Understanding this mechanism is crucial for accurate pharmacodynamic analysis of nitroglycerin.