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Journal of Pharmacology and Toxicology

Year: 2007  |  Volume: 2  |  Issue: 3  |  Page No.: 295 - 299

Molecular Modelling Analysis of the Metabolism of Meropenem

Fazlul Huq

Abstract

Meropenem (MER) is a new carbapenum antibiotic that is highly active in the treatment of a broad range of pathogenic infections including gram-positive and gram-negative bacteria. It is water-soluble and eliminated mainly by renal excretion, through both glomerular filtration and tubular secretion. MER is metabolized into open ring metabolite UK-1a which is also microbiologically active. In healthy volunteers, 70% of the administered dose is excreted as the unchanged drug and 20% as the metabolite UK-1a, in the urine. There is a significant reduction in renal excretory capacity for MER and its metabolite UK-1a in elderly subjects. Molecular modelling analyses based on molecular mechanics, semi-empirical and DFT calculations show that both MER and UK-1a have large LUMO-HOMO energy differences so that they would be kinetically inert. Also, neither MER nor UK-1a is found to abound in electron-deficient regions so that they would not readily react with glutathione and nucleobases in DNA. This may explain why the side-effects from MER-therapy are low.

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