Linked Life Data

837649

Source:http://linkedlifedata.com/resource/pubmed/id/837649

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1977-4-28
pubmed:abstractText
To study the influence of acute hepatic disease on the disposition of tolbutamide, we measured tolbutamide plasma protein binding and pharmacokinetic parameters after intravenous administration of the drug to 5 subjects during and after apparent recovery from acute viral hepatitis. Although during the acute phase of illness protein binding of the drug decreased in all, volume of distribution of tolbutamide (0.15 +/- 0.03 L/kg) did not change. Clearance based on total concentration of tolbutamide in plasma increased in all subjects during the acute phase of study (26 +/- 5.4 ml/hr/kg) in comparison to the recovery phase (18 +/- 2.8 ml/hr/kg, p less than 0.02). Protein binding decreased after unconjugated bilirubin was added to plasma from the recovery phase, but not to the extent observed during the acute phase of illness at comparable levels of bilirubin. Clearance based on unbound drug concentration, calculated by dividing the observed plasma clearance by the fraction of unbound drug in plasma, did not differ significantly between the 2 study phases (300 +/- 47 and 260 +/- 39 ml/hr/kg). These observations suggest that the increase in clearance based on total drug concentration in plasma during hepatitis can be attributed solely to decreased plasma binding. This decrease in binding may be attributed in part, but not entirely, to increased combination of bilirubin during illness. The concentration of unbound drug in plasma at steady-state is determined by the rate of drug administration and the clearance based on unbound drug. If this clearance does not change during hepatic disease, no dosage alterations for tolbutamide and other comparable drugs are necessary to maintain a constant concentration of unbound drug.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1977
pubmed:articleTitle
Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.