title: Enhancement of in vitro and in vivo microdialysis recovery of SB-265123 using Intralipid and Encapsin as perfusates.
abstract: 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.
authors.affiliation: Preclinical Drug Discovery, Cardiovascular & Urogenitary Centre of Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA. keith_w_ward@gsk.com
authors.forename: Keith W
authors.initials: KW
authors.lastname: Ward
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Medina
authors.forename: Samm T
authors.initials: ST
authors.lastname: Portelli
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Mahar Doan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Spengler
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ben
authors.forename: David
authors.initials: D
authors.lastname: Lundberg
authors.forename: Mark A
authors.initials: MA
authors.lastname: Levy
authors.forename: Emile P
authors.initials: EP
authors.lastname: Chen
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000085:Acetates / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000631:Aminopyridines / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D003505:Cyclodextrins / Q000378:metabolism*; D005217:Fat Emulsions, Intravenous / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D047392:beta-Cyclodextrins
chemical_list: D000085:Acetates; D000631:Aminopyridines; D003505:Cyclodextrins; D005217:Fat Emulsions, Intravenous; C121647:SB 265123; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin