INFLUENCE OF MONTELUKAST ON SPECIATION OF ESSENTIAL METAL IONS IN BLOOD PLASMA

Abstract

This study delves into the impact of Montelukast, a widely-used leukotriene receptor antagonist primarily employed in the clinical management of asthma, on the speciation of essential metal ions in blood plasma. We assess Montelukast’s ability to compete with plasma metal ions as well as other low molecular weight (LMM) ligands using a parameter known as the plasma mobilizing index (PMI). PMI is defined as the ratio between the total concentration of LMM-metal species in the presence and absence of this exogenous ligand in blood plasma. In the development of our computer model for blood plasma, we have taken significant steps to enhance the accuracy and comprehensiveness of the model. This includes incorporating a multi-phase model encompassing 10 different metals, 43 ligands, and over 6300 metal-ligand complexes. The total concentrations of all components have been meticulously sourced from a combination of peer-reviewed publications and authoritative Geigy tables. Nearly all stability constants pertaining to binary and ternary complexes have been obtained from well-regarded databases such as JESS, IUPAC, and NIST. In cases where necessary, these constants have been adapted to match physiological conditions. The findings from our study reveal intriguing insights. Montelukast exhibits a minimal effect on the distribution of calcium and magnesium ions, particularly at lower concentrations. However, its impact becomes more pronounced as concentrations increase, leading to a significant reduction in their presence. Montelukast also exerts a slight influence on the distribution of manganese ions, while consistently decreasing the concentration of zinc ions, with one specific type being an exception (ZnCysCit). Importantly, no discernible impact of Montelukast on the distribution of iron ions is observed. In conclusion, the comprehensive analysis conducted in this study suggests that Montelukast’s use remains safe concerning the metabolism of essential metal ions, especially within the context of its clinical applications in asthma management.