Clinical Pharmacokinetics and Pharmacodynamics of Colistin

Abstract : In this review, we give an updated summary on colistin pharmacokinetics and pharmacodynamics. Colistin is an old molecule that is frequently used as last line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Colistin is a decapeptide administered either as a prodrug, colistin methanesulfonate (CMS) when used intravenously, or as colistin sulfate when used orally. Because colistin binds to laboratory materials, many experimental issues are raised and studies on colistin can be tricky. Due to its large molecular weight and its cationic properties at physiological pH, colistin poorly passes through physiological membranes and is mainly distributed within the extracellular space. Renal clearance of colistin is very low, but the dosing regimen should be adapted to the renal function of the patient because CMS is partly eliminated by the kidney. Therapeutic drug monitoring of colistin is warranted because the pharmacokinetics of colistin is very variable, and because its therapeutic window is narrow. Resistance of bacteria to colistin is increasing worldwide in parallel to its clinical and veterinary uses and recently, a plasmid-mediated resistance mechanism (MCR-1) was described in animals and humans. In vitro, when exposed to colistin, bacteria develop various resistance mechanisms rapidly. The use of a loading dose might reduce the emergence of resistance but the use of colistin in combination also seems necessary.
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Clinical Pharmacokinetics, Springer Verlag, 2017, Epub ahead of print. 〈10.1007/s40262-017-0561-1〉
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Nicolas Grégoire, Vincent Aranzana-Climent, Sophie Magréault, Sandrine Marchand, William Couet. Clinical Pharmacokinetics and Pharmacodynamics of Colistin. Clinical Pharmacokinetics, Springer Verlag, 2017, Epub ahead of print. 〈10.1007/s40262-017-0561-1〉. 〈inserm-01528483〉

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