Enhancement of in vitro and in vivo microdialysis recovery of SB-265123 using Intralipid® and Encapsin® as perfusates

This study was conducted to compare the ability of two potential microdialysis perfusates to enhance the recovery of SB‐265123, a lipophilic, highly protein‐bound compound, both in vitro and in vivo. Initial in vitro experiments established that the recovery of SB‐265123 by microdialysis using norma...

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Bibliographic Details
Published in:Biopharmaceutics & drug disposition 2003-01, Vol.24 (1), p.17-25
Main Authors: Ward, Keith W., Medina, Sarah J., Portelli, Samm T., Mahar Doan, Kelly M., Spengler, Michael D., Ben, Michael M., Lundberg, David, Levy, Mark A., Chen, Emile P.
Format: Article
Language:English
Subjects:
2-Hydroxypropyl-beta-cyclodextrin
Acetates - blood
Acetates - chemistry
Acetates - metabolism
Aminopyridines - blood
Aminopyridines - chemistry
Aminopyridines - metabolism
Analysis
Animals
Area Under Curve
beta-Cyclodextrins
Biological and medical sciences
Cyclodextrins - metabolism
Encapsin
Fat Emulsions, Intravenous - metabolism
General pharmacology
Intralipid
Male
Medical sciences
microdialysis
Microdialysis - methods
pharmacokinetics
Pharmacology. Drug treatments
probe recovery
Rats
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Summary:This study was conducted to compare the ability of two potential microdialysis perfusates to enhance the recovery of SB‐265123, a lipophilic, highly protein‐bound compound, both in vitro and in vivo. Initial in vitro experiments established that the recovery of SB‐265123 by microdialysis using normal saline as a perfusate was poor (1.7%). Different concentrations of Intralipid® and Encapsin® also were evaluated in an identical in vitro setting, to determine enhancement of recovery. In vitro recovery was enhanced to approximately 24 and 65% with 5 and 20% Intralipid®, and to approximately 59 and 62% with 5 and 20% Encapsin®, respectively. A rat in vivo study was conducted with 20% Encapsin® to confirm the in vitro observations. In the in vivo study, 75–80% recovery of free SB‐265123 was achieved using 20% Encapsin® as a perfusate. The results from this study indicate that for SB‐265123, a lipophilic, highly protein‐bound molecule, Encapsin® is an efficient recovery enhancer in vitro. The results from this investigation further demonstrate that a recovery enhancer may be useful for in vivo applications, even with a compound that is highly bound to plasma protein. Copyright © 2002 John Wiley & Sons, Ltd.
ISSN:0142-2782
1099-081X
DOI:10.1002/bdd.332