Linked Life Data

8803875

Source:http://linkedlifedata.com/resource/pubmed/id/8803875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-12-5
pubmed:abstractText
Protein binding kinetics of basic antimicrobials including trimethoprim (TMP), erythromycin (EM), lincomycin (LM) and clindamycin (CM) were studied using porcine plasma, albumin and alpha 1-acid glycoprotein (AGP). Rosenthal plots of these basic drugs in porcine plasma suggest saturable and non-saturable binding. Dissociation constants (kd) and binding capacity (Bmax) for saturable binding were as follows: TMP, kd = 8.58 mumol/L, Bmax = 5.26 mumol/L; EM, kd = 2.72 mumol/L, Bmax = 3.06 mumol/L, LM, kd = 3.96 mumol/L, Bmax = 6.58 mumol/L and CM, kd = 4.43 mumol/L, Bmax = 21.7 mumol/L. The proportionality constants (Bmax2/kd2) for non-saturable binding were 0.29 in TMP, 0.52 in EM, 0.17 in LM and 3.2 in CM. The kds of the drugs in porcine AGP solution were determined by a fluorescence quenching method, using 1-anilino-8-naphthalene sulphonate (ANS) as a fluorescent probe: 9.51 mumol/L in TMP, 1.89 mumol/L in EM, 4.48 mumol/L in LM and 9.69 mumol/L, in CM. Comparable kd values between porcine plasma and AGP solution indicated that AGP is a major saturable binder in porcine plasma. Binding property to porcine albumin presented linearity, showing the following proportionality constants: 0.23 in TMP, 0.38 in EM, 0.01 in LM and 0.76 in CM. The comparable proportionality constants of TMP and EM between porcine plasma and albumin solution indicate that albumin is a major non-saturable binder, whereas proportionality constants of LM and CM in albumin solution compared to those in porcine plasma were low, implying another non-saturable binder, i.e. lipoprotein. Simulation curve of drug-binding percentage vs. AGP concentrations showed that in pigs under a pathologic state, or during early growth stage with high AGP levels, AGP could be a main contributor to drug-plasma protein binding for all drugs examined. The increase of AGP from normal to pathological concentrations induced a decrease in the unbound fraction: LM > CM > EM > TMP in order of AGP contribution to drug binding. Therefore, the disposition and efficacy of basic antimicrobials which bind to AGP with high affinity could be markedly influenced by altered AGP levels, implying AGP contribution to pharmacokinetics and pharmacodynamics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0140-7783
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
176-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Contribution of alpha 1-acid glycoprotein to plasma protein binding of some basic antimicrobials in pigs.
pubmed:affiliation
Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Japan.
pubmed:publicationType
Journal Article, Comparative Study