Linked Life Data

12685505

Source:http://linkedlifedata.com/resource/pubmed/id/12685505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-4-10
pubmed:abstractText
The aim of the present study was to determine (1) the extent of levocetirizine binding to human blood cells, plasma and individual plasma proteins; (2) the parameters for levocetirizine binding to individual plasma proteins both at their physiological concentrations and, for human serum albumin (HSA), at a lower saturating concentration; and (3) to simulate levocetirizine distribution in human blood using the information obtained at physiological haematocrit (H) for blood cells and at physiological concentrations for individual plasma proteins. The nature of the main binding sites of HSA, i.e. site I (warfarin) and site II (diazepam), preferentially involved in levocetirizine binding was also investigated. Over the range of therapeutic concentrations and multiples thereof, levocetirizine is extensively bound to blood components, the free fraction remaining constant (6.45%) and the fraction bound to blood cells and to plasma proteins accounting for 27.43 and 66.11%, respectively. The binding of levocetirizine to HSA in the presence of physiological concentrations of non-esterified fatty acids (NEFAs) is the main interaction of levocetirizine in blood (50.68% of overall blood binding). This interaction is fatty acid sensitive, with decreasing concentrations of NEFA increasing the amount of bound drug and vice versa. Levocetirizine is also bound to alpha1-acid-glycoprotein and high-density lipoproteins (5.17 and 6.89% of overall blood binding, respectively). The displacement of levocetirizine by diazepam is consistent with the binding of this drug to HSA at site II, as diazepam is a specific marker for this site. The binding of levocetirizine to HSA at site II being characterized by a low association constant, other drugs sharing the same site with high association constants cannot displace levocetirizine except at very high plasma concentrations. In any case, at therapeutic concentrations of levocetirizine and at physiological protein concentrations, the observation that none of the levocetirizine binding proteins is saturated suggests that very little or no variation of the free fraction will occur although a different distribution of its bound forms is possible.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0767-3981
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
471-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12685505-Acetic Acids, pubmed-meshheading:12685505-Adult, pubmed-meshheading:12685505-Binding, Competitive, pubmed-meshheading:12685505-Blood Cells, pubmed-meshheading:12685505-Blood Proteins, pubmed-meshheading:12685505-Cetirizine, pubmed-meshheading:12685505-Dialysis, pubmed-meshheading:12685505-Drug Interactions, pubmed-meshheading:12685505-Female, pubmed-meshheading:12685505-Histamine H1 Antagonists, pubmed-meshheading:12685505-Humans, pubmed-meshheading:12685505-Lipoproteins, HDL, pubmed-meshheading:12685505-Lipoproteins, LDL, pubmed-meshheading:12685505-Lipoproteins, VLDL, pubmed-meshheading:12685505-Male, pubmed-meshheading:12685505-Middle Aged, pubmed-meshheading:12685505-Piperazines, pubmed-meshheading:12685505-Protein Binding, pubmed-meshheading:12685505-Serum Albumin, pubmed-meshheading:12685505-Warfarin
pubmed:year
2002
pubmed:articleTitle
Blood distribution of levocetirizine, a new non-sedating histamine H1-receptor antagonist, in humans.
pubmed:affiliation
Laboratoire de Pharmacologie, Faculté de Médecine, Créteil-Cedex, France. bree@univ-paris12.fr
pubmed:publicationType
Journal Article, Comparative Study, In Vitro