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.

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

“…Depending on the lipophilicity of the drug, the perfusate medium may have to be modified to allow more lipophilic substances to enter the probe. Substances such as albumin, Intralipid and Encapsin have been used [14,15] . The enhancing effect of adding binding agents such as ␣ -, ␤ -and ␥ -cyclodextrins to the perfusate has been evaluated by studying the recovery of several eicosanoids in vitro [16] .…”

Effect of glycyrrhizic acid on rhein renal penetration: a microdialysis study in rats

“…Several proposed strategies for improving recovery of lipophilic compounds include the addition of binding agents like albumin (Kirbs & Kloft, 2014) or hydroxypropyl-b-cyclodextrin (May et al, 2013) to the perfusate. Additional strategies include the use of isotonic lipoemulsions (Ward et al, 2003) and optimization of the perfusate pH (Tre et al, 2012). In the present study, a 20% ethanol-Ringer's was used as the perfusate solution, thus improving the microdialysis RH recovery (data not shown).…”

Bioequivalence for Topical Products—An Update

“…Recoveries are low for highly lipophil- ic and highly protein-bound drugs. This problem can be overcome to some extent by using solubilizers such as albumin, Intralipid®, Encapsin® (70,71), cyclodextrins and cosolvents like ethanol, propylene glycol and dimethylsulfoxide (72). Recoveries of lipophilic drugs can also be affected due to drug binding to the probe material (73).…”