Linked Life Data

2720699

Source:http://linkedlifedata.com/resource/pubmed/id/2720699

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-7-13
pubmed:abstractText
Eleven parkinsonian patients participated in a pharmacokinetic/pharmacodynamic study in an attempt to model levodopa (L-DOPA) plasma concentrations to clinical effect. Carbidopa 25 mg/L-DOPA 100 mg (Sinemet 25/100) was given orally, and blood samples were obtained before and serially for 4 hours after the dose. Effect measurements were obtained with each blood sample and included tapping score, timed walking, and global assessment of motor function. Mean L-DOPA plasma concentrations were fitted to a one-compartment pharmacokinetic model. A time-wise plot of modeled plasma L-DOPA concentrations versus mean effect measurements revealed a counter-clockwise hysteresis. Effect compartment concentrations were determined by a least squares approach, which determined elimination rate constants by minimizing hysteresis. Half-times for the equilibration between plasma and the effect compartment were 0.39 h for tapping, 0.36 h for walking, and 0.34 h for the global score. Pharmacodynamic data were fit best with an Emax model with baseline effect for tapping (Emax = 53.2 taps/60 s, EC50 = 0.58 microgram/ml) and global score (Emax set at 5.0 by limits of scale, EC50 = 2.53 micrograms/ml). A linear model best described the relationship between predicted effect site concentration and timed walking. L-DOPA plasma concentrations after oral Sinemet did not correlate well with clinical response because clinical response lags behind plasma concentrations. Half-times for equilibration between plasma and the effect site were similar for all of the effects measured.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0362-5664
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-7
pubmed:dateRevised
2009-10-6
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Pharmacokinetic and pharmacodynamic modeling of L-dopa plasma concentrations and clinical effects in Parkinson's disease after Sinemet.
pubmed:affiliation
College of Pharmacy and Allied Health, Wayne State University, Detroit, Michigan 48202.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't