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- W1977358613 abstract "Abstract Objectives LK-157 is a novel 10-ethylidene tricyclic carbapenem that resembles the structure of the broad-spectrum antibiotic sanfetrinem and acts as a potent inactivator of β-lactamases of classes A, C and D. LK-157 is a highly soluble but poorly permeable drug. Since most of the β-lactams are poorly absorbed, ester prodrugs LK-159, LK-157E1 and LK-157E2 were designed to enhance membrane permeability. This study investigated the permeability of LK-157 and the three ester prodrugs across rat intestine in vitro. The morpholinoethyl ester of sanfetrinem was also investigated. Method Permeability across rat jejunum was determined using EasyMount side-by-side diffusion chambers. Key findings The solubility and permeability of morpholinoethyl ester LK-157E2 were superior to those of LK-159 and LK-157E1. The morpholinoethyl ester of sanfetrinem LK-176E1 had the highest observed permeability coefficient and consequently the highest predicted absorption in humans. Conclusions These results suggest that the morpholinoethyl esters of LK-157 and sanfetrinem could be further investigated to assess bioavailability in vivo." @default.
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- W1977358613 date "2009-09-01" @default.
- W1977358613 modified "2023-10-14" @default.
- W1977358613 title "Permeability of a novel β-lactamase inhibitor LK-157 and its ester prodrugs across rat jejunum in vitro" @default.
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- W1977358613 doi "https://doi.org/10.1211/jpp.61.09.0011" @default.
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