Linked Life Data

17624700

Source:http://linkedlifedata.com/resource/pubmed/id/17624700

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2007-9-3
pubmed:abstractText
Benzimidazole 2-carbamates, such as albendazole (ABZ) and mebendazole (MBZ), used for the treatment of helmintic infections, have low aqueous solubility and poor bioavailability, both of which lead to high interindividual variability when used for human systemic helmintiosis; therefore, it is necessary to search for new anthelmintics with better biopharmaceutical properties. In the present study the solubility, pKa, logP and apparent permeability in the Caco-2 cells system of four novel anthelmintic (1H-benzimidazol-5(6)-yl)carboxamide derivatives (compounds 1-4) with a 2-methylthyo group were evaluated. Also the pharmacokinetic parameters of compound 1 which in previous studies showed activity similar to ABZ against T. spirallis, was evaluated in BALB/c mice, as a representative molecule of the series. The novel anthelmintics, showed better solubility than ABZ in aqueous acid pH and in organic solvents. The logP, P(app) and Caco-2 data indicate that the 4 derivatives are highly permeable drugs, but it is possible that an efflux system could be involved in the transport of these compounds. Plasma levels of compound 1 and its sulfoxide (compound 5) were high after the first 5 min. This fact strongly suggests that compound 1 is rapidly metabolized in the small intestine. On the other hand, the sulfone metabolite (compound 6) levels were lower than those of compound 5. The half life and mean residence time (MRT) of compound 1 and its main metabolites indicate that their elimination is very rapid. More studies in mammalian species are necessary in order to understand the pharmacokinetic behavior of these novel compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0378-5173
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
343
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-65
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Biopharmaceutic evaluation of novel anthelmintic (1H-benzimidazol-5(6)-yl)carboxamide derivatives.
pubmed:affiliation
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't