Linked Life Data

20218014

Source:http://linkedlifedata.com/resource/pubmed/id/20218014

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-3-11
pubmed:abstractText
We have studied by digital computer simulation the effect of concentration-dependent plasma protein and tissue binding on the time course of drug concentrations (both unbound and total) in plasma following rapid injection of a drug whose elimination rate is proportional to either free or total drug concentration in plasma, assuming instantaneous equilibration of the drug between vascular and nonvascular spaces. The following observations were made when elimination rate was assumed to be a function of free drug concentration: (a) when plasma protein binding is nonlinear and there is either no tissue binding or linear tissue binding, log concentration-time plots of free drug are always concave whereas such plots for total (sum of free and bound) drug can be convex, almost linear, or concave (apparently biexponential) depending on the plasma protein binding parameters relative to the initial concentration; (b) linear tissue binding in association with nonlinear plasma protein binding can reduce the concavity or enhance the convexity of log total concentration-time plots. When drug elimination rate was assumed to be a function of total concentration in plasma, nonlinear plasma protein binding in association with linear or no tissue binding yielded convex log total concentration-time plots which could sometimes be described by Michaelis-Menten kinetics. In general, drug concentration-dependent changes in the apparent volume of distribution resulting from nonlinear plasma protein and (where applicable) tissue binding have a pronounced effect on the slope of log total plasma concentration-time plots. It appears that under clinically realistic conditions an otherwise marked curvature of such plots, due to nonlinear plasma protein binding, may in fact be dampened or overcome by linear tissue binding.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0090-466X
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-206
pubmed:meshHeading
pubmed:year
1979
pubmed:articleTitle
Effect of plasma protein and tissue binding on the time course of drug concentration in plasma.
pubmed:affiliation
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Amherst, New York 14260, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural