Linked Life Data

9379352

Source:http://linkedlifedata.com/resource/pubmed/id/9379352

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1997-11-10
pubmed:abstractText
A physiologically based pharmacokinetic model for basic drugs has been established on the basis of octanol-water partition coefficients of the non-ionized, unbound drugs (Poct). The parameters for the physiological model in man were estimated from a regression equation obtained for the relationships between the Poct and the tissue-plasma partition coefficient, the hepatic intrinsic clearance (CLint,h) and the blood-to-plasma concentration ratio in rabbits. The plasma concentrations observed after intravenous administration of ten basic drugs (3.2 mg kg-1) to rabbits agreed with the levels predicted using the physiological model (r = 0.710-0.980). In man, the predicted plasma concentrations of basic drugs were in good agreement with reported values (r = 0.729-0.973), except for diazepam and pentazocine. Variations in plasma and brain-concentration profiles of clomipramine and nitrazepam in various disease states were simulated using the model. We assumed that the changes in unbound fraction of drug in serum (fp), CLint,h and the hepatic blood flow rate were from 0.25- to 4-fold that of the control and that fat volume changed by 0.2- to 5-fold. With regard to changes in fp, we predicted that the brain-plasma concentration ratio of clomipramine was 1.5- to 25-fold that of the control 24 h after intravenous administration, although the variations in the plasma concentration-time profiles were less marked. Plasma concentrations predicted for several basic drugs were in good agreement with reported values and this physiological model could be useful for predicting drug-disposition kinetics in man.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3573
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
762-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Prediction of changes in the clinical pharmacokinetics of basic drugs on the basis of octanol-water partition coefficients.
pubmed:affiliation
Hospital Pharmacy, Graduate School of Pharmaceutical Sciences, Kanazawa University, Japan.
pubmed:publicationType
Journal Article