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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Demonstration of Interaction between Carbapenem Group Antibiotics and Different Immunosuppressant Drugs by Molecular Docking

Author(s): Deniz Karatas, Ataman Gonel*, Ismail Koyuncu, Ebru Temiz, Kadir Egi, Mustafa Durgun, Sukru Akmese and Murat Caglayan

Volume 21, Issue 5, 2024

Published on: 21 March, 2023

Page: [880 - 887] Pages: 8

DOI: 10.2174/1570180820666230224104658

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Abstract

Background: It has been shown that drugs used parenterally cause errors in immunosuppressant concentrations measured by LC-MS / MS method. It is yet unknown whether this measurement error is due to drug-drug interaction or analytical interference.

Objective: The aim of this study is to investigate the possible interaction and inhibition concentrations of broad-spectrum antibiotics (ertapenem, meropenem, imipenem) with 4 different immunosuppressants (tacrolimus, sirolimus, everolimus, cyclosporine A) by molecular docking.

Methods: The docking results of ertapenem, meropenem, and imipenem-cilastatin drugs, which are frequently used in intensive care units and wards, were analyzed with the Autodock 4.2 program. Binding energy levels and inhibition concentrations were recorded.

Results: The highest binding energies of the most stable conformations, providing the best compatibility among the active ingredients, belong to cilastatin. The interaction energy of cilastatin with sirolimus in 320 conformations was calculated as -4.08 kcal/mol. Sirolimus interacted with ertapenem at -3.43, imipenem at -2.53, and meropenem at -3.84 kcal/mol. According to these values, the receptor, which is the most compatible host with all ligand molecules, is sirolimus. The least interaction energy value was calculated between cyclosporine and imipenem (-1.12 kcal / mol).

Conclusion: Concerning the most stable conformations of models docked with Autodock tools, it has been determined that carbapenems interact with immunosuppressants. Since the detected inhibition concentration levels can be seen in blood samples taken immediately after carbapenem injection, immunosuppressant measurement is recommended before the use of carbapenem in immunosuppressant monitoring of transplant patients.

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