Linked Life Data

15634032

Source:http://linkedlifedata.com/resource/pubmed/id/15634032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-6
pubmed:abstractText
Glucocorticoids have pleiotropic effects that are used to treat diverse diseases such as asthma, rheumatoid arthritis, systemic lupus erythematosus and acute kidney transplant rejection. The most commonly used systemic glucocorticoids are hydrocortisone, prednisolone, methylprednisolone and dexamethasone. These glucocorticoids have good oral bioavailability and are eliminated mainly by hepatic metabolism and renal excretion of the metabolites. Plasma concentrations follow a biexponential pattern. Two-compartment models are used after intravenous administration, but one-compartment models are sufficient after oral administration.The effects of glucocorticoids are mediated by genomic and possibly nongenomic mechanisms. Genomic mechanisms include activation of the cytosolic glucocorticoid receptor that leads to activation or repression of protein synthesis, including cytokines, chemokines, inflammatory enzymes and adhesion molecules. Thus, inflammation and immune response mechanisms may be modified. Nongenomic mechanisms might play an additional role in glucocorticoid pulse therapy. Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics. Pharmacokinetic parameters such as the elimination half-life, and pharmacodynamic parameters such as the concentration producing the half-maximal effect, determine the duration and intensity of glucocorticoid effects. The special contribution of either of these can be distinguished with pharmacokinetic/pharmacodynamic analysis. We performed simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous cortisol as biomarkers for the effects of methylprednisolone. These simulations suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocorticoid administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0312-5963
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-98
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.
pubmed:affiliation
Division of Nephrology, University Hospital Ulm, Robert-Koch-Str. 8, Ulm 89081, Germany.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't