Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The purpose of this study was to assess the effect of biorelevant apical conditions on intestinal permeability estimation in the Caco-2 system for amprenavir, a poorly water-soluble substrate of the efflux carrier
P-glycoprotein
(
P-gp
). To establish biorelevant conditions, human intestinal fluids (HIF) were aspirated from the duodenum and jejunum in fasted subjects, before and during 4 h after the intake of a standard formulation of amprenavir (
Agenerase
). The HIF samples were characterized with respect to the concentrations of phospholipids, individual bile salts, amprenavir, and the excipient d-alpha-tocopheryl polyethyleneglycol 1000 succinate (TPGS); subsequently, the use of these samples in the Caco-2 system during permeability estimation for amprenavir was compared to standard conditions (amprenavir 10 microM dissolved in HBSS-based transport medium). The presence of the solubilizing excipient TPGS resulted in high intraluminal amprenavir concentrations (mM-range) and affected the permeability in a concentration-dependent way. At the observed intraluminal TPGS concentrations (mM-range), TPGS appeared to completely inhibit the interaction between amprenavir and
P-gp
, suggesting that the effect of
P-gp
on transepithelial transport of amprenavir in a clinical setting is probably negligible. This study illustrates the importance of the evaluation of intraluminal conditions after drug intake and their integration in permeability estimation in vitro.
...
PMID:Intraluminal drug and formulation behavior and integration in in vitro permeability estimation: a case study with amprenavir. 1637 52
