Intravenous microdialysis sampling in awake, freely-moving rats.
Intravenous microdialysis sampling in the awake, freely-moving rat for the determination of free drug concentrations in blood is described. Intravenous microdialysis was performed with a nonmetallic, flexible dialysis probe. The pharmacokinetics of theophylline were determined using both microdialysis sampling and collection of whole blood following an iv dose. There was no difference in the half-life of elimination of theophylline determined by microdialysis, 4.4 +/- 0.4 h, and whole blood sampling, 4.5 +/- 0.7 h. The kinetics of elimination were affected by removing blood samples and by using anesthesia. The half-life of elimination was 4.4 +/- 0.4 h when using simultaneous microdialysis and whole-blood sampling and only 3.0 +/- 0.4 h using microdialysis alone. The half-life of elimination was 17.0 +/- 7.1 h in chloral hydrate anesthesized rats. Microdialysis samples were continuously collected for over 7 h without fluid loss using a single experimental animal. Microdialysis sampling directly assesses the free drug concentration in blood. The extent of theophylline binding to blood proteins was determined in vitro in rat plasma and rat whole blood using both ultrafiltration and microdialysis. Theophylline was (47.3 +/- 1.3)% bound in rat plasma and (52.2 +/- 1.6)% bound in rat whole blood. Microdialysis sampling is a powerful tool for pharmacokinetic studies, providing accurate and precise pharmacokinetic data.
Telting-Diaz
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Department of Chemistry, University of Kansas, Lawrence 66045.
Scott
D O
DO
Lunte
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CE
D000758:Anesthesia; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D001800:Blood Specimen Collection / Q000379:methods*; D002853:Chromatography, Liquid; D003956:Dialysis / Q000379:methods*; D006207:Half-Life; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*
D001798:Blood Proteins; D013806:Theophylline