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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1980-2-15
pubmed:abstractText
The purpose of this investigation was to study, by digital computer stimulation, the accumulation kinetics of drugs which exhibit concentration-dependent binding to tissues and either linear (constant free fraction) or concentration-dependent (increasing free action with increasing drug concentration) binding to plasma proteins. It was assumed that elimination rate is proportional to free drug concentration in plasma and that there occurs instantaneous equilibration of drug between vascular and nonvascular spaces. Nonlinear binding can yield, under certain conditions, apparently biexponential plasma concentration-time curves which may be misinterpreted as being representative of a linear and biexponential system. Such misinterpretation would cause the following errors in the prediction of drug accumulation and elimination kinetics during and after constant-rate infusion: (a) the time required to reach steady state may be overestimated, and (b) the prominence of the apparent distribution phase after cessation of infusion may be underestimated. Drugs with linear and nonlinear plasma protein binding characteristics differ with respect to the relaionship between infusion rate and steady-state concentration. This relationship is linear when plasma protein binding is linear. Steady-state concentration increases less than proportionally with increasing infusion rate if plasma protein binding is drug concentration dependent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0090-466X
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
397-405
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1979
pubmed:articleTitle
Accumulation kinetics of drugs with nonlinear plasma protein and tissue binding characteristics.
pubmed:publicationType
Journal Article