Abstract:
:The purpose of this research was to combine microdialysis sampling techniques with a highly sensitive radioimmunoassay (RIA) to study the in vivo kinetic response of pharmacologically important substances. This technique allowed for a dense sampling regimen from an awake, free-roaming experimental animal with no loss of blood and with rapid analysis of the dialysate. An important methodological criterion for accurate quantitation of a test drug in the extracellular space was knowledge of the relative recovery of the sampling system at the time of experimentation. Accordingly, the factors which influenced the recovery of drug during dense in vivo microdialysis sampling were examined and an analytical technique was developed to measure the instantaneous recovery of drug from the extracellular space. This information was applied to in vivo (iv) sampling experiments on anaesthetized and awake, free-roaming rats following bolus and multiple long-term iv administrations of the highly protein bound steroid (i.e. greater than 90%), hydrocortisone-21-phosphate. These studies indicated that unbound hydrocortisone levels as determined by the RIA-linked microdialysis (RIALM) technique fluctuated rapidly between each 2-min sampling interval, but nevertheless decreased to predose endogenous concentrations in a first-order fashion (t1/2 = 17-29 min). The rapid fluctuations of unbound hydrocortisone may reflect real pharmacokinetic or pharmacodynamic phenomena, attributed, perhaps, to reequilibration of the unbound drug pool with proteins and tissues in the blood.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Miller MA,Geary RSdoi
10.1016/0731-7085(91)80021-zsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
901-10issue
10-12eissn
0731-7085issn
1873-264Xpii
0731-7085(91)80021-Zjournal_volume
9pub_type
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
pub_type: 杂志文章
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journal_title:Journal of pharmaceutical and biomedical analysis
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journal_title:Journal of pharmaceutical and biomedical analysis
pub_type: 杂志文章
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