• Je něco špatně v tomto záznamu ?

Caco-2 cells and Biopharmaceutics Classification System (BCS) for prediction of transepithelial transport of xenobiotics (model drug: caffeine)

L. Smetanova, V. Stetinova, D. Kholova, J. Kvetina, J. Smetana, Z. Svoboda

. 2009 ; 30 Suppl 1 () : 101-105.

Jazyk angličtina Země Švédsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc12025387

OBJECTIVES: The Caco-2 cell monolayer model is widely used as a standard screening tool for studying the mechanisms of cellular drug transport. Caffeine was chosen as a model drug and is supposed to be class I of the Biopharmaceutics Classification System (BCS). Our study was conducted 1) to characterize the mechanisms of caffeine transport across the intestinal barrier, 2) to classify caffeine according to BCS, 3) to predict drugs intestinal absorption in humans. METHODS: Caffeine transport (0.1, 0.3, 1 and 10 mmol/l) was studied in Caco-2 cell monolayer in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under iso-pH 7.4 and pH-gradient (6/7.4) conditions. The relative contribution of the paracellular route was estimated using Ca2+- free transport medium (opening tight junctions). RESULTS: The caffeine transport was linear with time, transport direction and pH independent, displaying non-saturable (first-order) kinetics, with high permeability coefficient (Papp): in AP-BL direction Papp = 46.3-53.5 x 10-6 cm/s; in BL-AP direction Papp = 45.6-49.4 x 10-6 cm/s. Thus, the transport seems to be transcellular mediated by passive diffusion. Using Ca2+- free transport medium tight junctions were opened (confirmed by increased Papp of mannitol) but the caffeine Papp was not changed. Thus, the paracellular route is only a minor way of caffeine transport. CONCLUSION: High solubility and high permeability of caffeine rank it among class I of BCS and well absorbed compounds.

000      
00000naa a2200000 a 4500
001      
bmc12025387
003      
CZ-PrNML
005      
20130128213352.0
007      
ta
008      
120816s2009 sw f 000 0#eng||
009      
AR
035    __
$a (PubMed)20027153
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sw
100    1_
$a Smetanová, Libuše $7 xx0139464 $u Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, Czech Republic. smetanova@uebf.cas.cz
245    10
$a Caco-2 cells and Biopharmaceutics Classification System (BCS) for prediction of transepithelial transport of xenobiotics (model drug: caffeine) / $c L. Smetanova, V. Stetinova, D. Kholova, J. Kvetina, J. Smetana, Z. Svoboda
520    9_
$a OBJECTIVES: The Caco-2 cell monolayer model is widely used as a standard screening tool for studying the mechanisms of cellular drug transport. Caffeine was chosen as a model drug and is supposed to be class I of the Biopharmaceutics Classification System (BCS). Our study was conducted 1) to characterize the mechanisms of caffeine transport across the intestinal barrier, 2) to classify caffeine according to BCS, 3) to predict drugs intestinal absorption in humans. METHODS: Caffeine transport (0.1, 0.3, 1 and 10 mmol/l) was studied in Caco-2 cell monolayer in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under iso-pH 7.4 and pH-gradient (6/7.4) conditions. The relative contribution of the paracellular route was estimated using Ca2+- free transport medium (opening tight junctions). RESULTS: The caffeine transport was linear with time, transport direction and pH independent, displaying non-saturable (first-order) kinetics, with high permeability coefficient (Papp): in AP-BL direction Papp = 46.3-53.5 x 10-6 cm/s; in BL-AP direction Papp = 45.6-49.4 x 10-6 cm/s. Thus, the transport seems to be transcellular mediated by passive diffusion. Using Ca2+- free transport medium tight junctions were opened (confirmed by increased Papp of mannitol) but the caffeine Papp was not changed. Thus, the paracellular route is only a minor way of caffeine transport. CONCLUSION: High solubility and high permeability of caffeine rank it among class I of BCS and well absorbed compounds.
650    _2
$a biologický transport $x účinky léků $x fyziologie $7 D001692
650    _2
$a Caco-2 buňky $7 D018938
650    _2
$a kofein $x farmakokinetika $x farmakologie $7 D002110
650    _2
$a buněčné kultury $7 D018929
650    _2
$a viabilita buněk $x účinky léků $7 D002470
650    _2
$a difuze $7 D004058
650    _2
$a lidé $7 D006801
650    _2
$a koncentrace vodíkových iontů $7 D006863
650    _2
$a intestinální absorpce $7 D007408
650    _2
$a střevní sliznice $x metabolismus $7 D007413
650    _2
$a kinetika $7 D007700
650    _2
$a lineární modely $7 D016014
650    _2
$a mannitol $x metabolismus $7 D008353
650    _2
$a permeabilita $x účinky léků $7 D010539
650    _2
$a těsný spoj $x účinky léků $x metabolismus $7 D019108
650    _2
$a xenobiotika $x farmakokinetika $x farmakologie $7 D015262
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Štětinová, Věra $7 xx0117623
700    1#
$a Kholová, Dagmar. $7 _AN036648
700    1_
$a Květina, Jaroslav, $d 1930- $7 jk01071205
700    1_
$a Smetana, Jan
700    1_
$a Svoboda, Zbyněk $7 xx0081965
773    0_
$w MED00168352 $t Neuro endocrinology letters $x 0172-780X $g Roč. 30 Suppl 1(2009), s. 101-105
856    41
$u https://pubmed.ncbi.nlm.nih.gov/20027153 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y m
990    __
$a 20120816 $b ABA008
991    __
$a 20130128213530 $b ABA008
999    __
$a ok $b bmc $g 947429 $s 782733
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2009 $b 30 Suppl 1 $d 101-105 $i 0172-780X $m Neuro-endocrinology letters $n Neuro-endocrinol. lett. $x MED00168352
LZP    __
$a Pubmed-20120816/10/02

Najít záznam

Citační ukazatele

Možnosti archivace