Permeability of a novel beta-lactamase inhibitor LK-157 and its ester prodrugs across rat jejunum in vitro

Autor:	Petra, Iglicar, Igor, Legen, Gregor, Vilfan, Lovro, Selic, Andrej, Prezelj
Rok vydání:	2009
Předmět:	Male Lactams Molecular Structure Morpholines Esters In Vitro Techniques Permeability Anti-Bacterial Agents Rats Surface-Active Agents Jejunum Carbapenems Solubility Solvents Animals Prodrugs Rats Wistar beta-Lactamase Inhibitors
Zdroj:	The Journal of pharmacy and pharmacology. 61(9)
ISSN:	0022-3573
Popis:	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 beta-lactamases of classes A, C and D. LK-157 is a highly soluble but poorly permeable drug. Since most of the beta-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.Permeability across rat jejunum was determined using EasyMount side-by-side diffusion chambers.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.These results suggest that the morpholinoethyl esters of LK-157 and sanfetrinem could be further investigated to assess bioavailability in vivo.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::a73fda8de9da97c24c57837fccfda14f https://pubmed.ncbi.nlm.nih.gov/19703371 Zobrazit plný text záznamu Plný text