PMID- 19491029
OWN - NLM
STAT- MEDLINE
DCOM- 20090824
LR  - 20131121
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 37
IP  - 3-4
DP  - 2009 Jun 28
TI  - Impact of carriers in oral absorption: Permeation across Caco-2 cells for the 
      organic anions estrone-3-sulfate and glipizide.
PG  - 378-86
LID - 10.1016/j.ejps.2009.03.008 [doi]
AB  - Carriers may mediate the permeation across enterocytes for drug substances being 
      organic anions. Carrier mediated permeation for the organic anions 
      estrone-3-sulfate (ES) and glipizide across Caco-2 cells were investigated 
      kinetically, and interactions on involved carriers evaluated. Initial uptakes 
      (P(UP)) at apical and basolateral membranes, apparent permeabilities (P(APP)) and 
      corresponding intracellular end-point accumulations (P(EPA)) of radioactive 
      labeled compounds were studied. Possible effects of other anionic compounds were 
      investigated. Apical P(UP) and absorptive P(APP) for ES were inhibited and its 
      absorptive P(EPA) prevented in presence of the investigated organic anions and 
      apical P(UP) was saturable with K(m) 23microM. Basolateral P(UP) and exsorptive 
      P(APP) were inhibited, its exsorptive P(EPA) was prevented, and basolateral P(UP) 
      and exsorptive P(APP) were saturable with K(m) 44microM and 38microM, 
      respectively. BCRP inhibition affected both absorptive an exsorptive P(EPA) and 
      P(APP) for ES. Glipizide apical P(UP) and absorptive P(APP) were not inhibitable. 
      Basolateral P(UP) for glipizide was inhibitable, its P(EPA) prevented, and P(UP) 
      was saturable with K(m) 56microM, but exsorptive P(APP) was not affected. Carrier 
      mediated exsorption kinetics for ES are seen at both apical and basolateral 
      membranes, resulting in predominant exsorption despite presence of absorptive 
      carrier(s). Carrier mediated basolateral P(UP) for glipizide was observed, but 
      glipizide P(APP) was not described by carrier kinetics. However, glipizide is 
      affecting exsorption for ES, due to interactions on basolateral carrier. The 
      study confirms that estrone-3-sulfate can be used to characterize anionic carrier 
      kinetics. Furthermore it is suggested that estrone-3-sulfate may be used to 
      identify compounds which may interact on anionic carriers.
FAU - Gram, Luise K
AU  - Gram LK
AD  - Molecular Biopharmaceutics, Department of Pharmaceutics and Analytical Chemistry, 
      Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, 
      Denmark.
FAU - Rist, Gerda Marie
AU  - Rist GM
FAU - Lennernas, Hans
AU  - Lennernas H
FAU - Steffansen, Bente
AU  - Steffansen B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090325
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Estrogens, Conjugated (USP))
RN  - 0 (Hypoglycemic Agents)
RN  - 2DI9HA706A (Estrone)
RN  - QTL48N278K (estrone sulfate)
RN  - X7WDT95N5C (Glipizide)
SB  - IM
MH  - Absorption
MH  - Administration, Oral
MH  - Caco-2 Cells
MH  - Cell Membrane Permeability
MH  - Estrogens, Conjugated (USP)/administration & dosage/*pharmacokinetics
MH  - Estrone/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Glipizide/administration & dosage/*pharmacokinetics
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Hypoglycemic Agents/administration & dosage/*pharmacokinetics
EDAT- 2009/06/06 09:00
MHDA- 2009/08/25 09:00
CRDT- 2009/06/04 09:00
PHST- 2008/05/29 00:00 [received]
PHST- 2009/03/11 00:00 [revised]
PHST- 2009/03/12 00:00 [accepted]
PHST- 2009/06/04 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/08/25 09:00 [medline]
AID - S0928-0987(09)00083-9 [pii]
AID - 10.1016/j.ejps.2009.03.008 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2009 Jun 28;37(3-4):378-86. doi: 10.1016/j.ejps.2009.03.008. 
      Epub 2009 Mar 25.