This study aimed i) to characterize the transepithelial transport of the mucolytic agent ambroxol hydrochloride across the intestinal barrier, ii) to classify the ambroxol according to Biopharmaceutics Classification System (BCS) and iii) to predict ambroxol absorption in humans. Transport of ambroxol (100, 300 and 1000 micromol/l) was studied in a human colon carcinoma cell line Caco-2 in apical to basolateral and basolateral to apical direction, under iso-pH 7.4 and pH-gradient (6 vs. 7.4) conditions. The relative contribution of the paracellular route was estimated using Ca2+-free transport medium. Ambroxol samples from receiver compartments were analysed by HPLC with UV detection (242 nm). Results showed that ambroxol transport is linear with time, pH-dependent and direction-independent, displays non-saturable (first-order) kinetics. Thus, the transport seems to be transcellular mediated by passive diffusion. Estimated high solubility and high permeability (P(app) = 45 x 10(-6) cm/s) of ambroxol rank it among well absorbed compounds and class I of BCS. It can be expected that the oral dose fraction of ambroxol absorbed in human intestine is high.
- MeSH
- absorpce MeSH
- ambroxol aplikace a dávkování farmakokinetika klasifikace MeSH
- biologické modely MeSH
- epitel metabolismus MeSH
- expektorancia aplikace a dávkování farmakokinetika klasifikace MeSH
- karcinom metabolismus MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lineární modely MeSH
- nádorové buněčné linie MeSH
- nádory tračníku metabolismus MeSH
- permeabilita MeSH
- rozpustnost MeSH
- ultrafialové záření MeSH
- vápník nedostatek MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
