PMID- 27416295
OWN - NLM
STAT- MEDLINE
DCOM- 20170328
LR  - 20181202
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 30
IP  - 6
DP  - 2016 Dec
TI  - Intestinal permeability and P-glycoprotein-mediated efflux transport of 
      ticagrelor in Caco-2 monolayer cells.
PG  - 577-584
LID - 10.1111/fcp.12219 [doi]
AB  - Ticagrelor is the unique reversible oral antiplatelet drug commercialized today. 
      During this study, the intestinal permeability of ticagrelor and its potential 
      P-glycoprotein (P-gp)-mediated active transport were assessed. To this end, 
      bidirectional transport of ticagrelor was performed across Caco-2 (human 
      epithelial colorectal adenocarcinoma) monolayer model in the presence and absence 
      of potent P-gp inhibitor valspodar. Ticagrelor presented an apical-basolateral 
      apparent permeability coefficient (P(app) ) of 6.0 x 10(-6) cm/s. On the other 
      hand, mean efflux ratio (ER) of 2.71 was observed for ticagrelor describing a 
      higher efflux permeability compared to the influx component. Valspodar showed a 
      significant inhibitory effect on the efflux of ticagrelor suggesting involvement 
      of P-gp in its oral disposition. Co-incubation of the P-gp inhibitor decreased 
      the efflux P(app) of ticagrelor from 1.60 x 10(-5) to 1.13 x 10(-5) cm/s and 
      decreased its ER by 70%. Results suggest a modest active transport of ticagrelor 
      by P-gp across the Caco-2 cell monolayer. The co-administration of ticagrelor 
      with a P-gp inhibitor seems altogether unlikely to have an extended impact on 
      pharmacokinetics of ticagrelor and cause bleeding events in patients.
CI  - (c) 2016 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Marsousi, Niloufar
AU  - Marsousi N
AD  - Clinical Pharmacology and Toxicology Service, Geneva University Hospitals, Rue 
      Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland.
AD  - School of pharmaceutical sciences, Geneva University, Rue Michel Servet 1, 1211, 
      Geneva, Switzerland.
FAU - Doffey-Lazeyras, Fabienne
AU  - Doffey-Lazeyras F
AD  - Clinical Pharmacology and Toxicology Service, Geneva University Hospitals, Rue 
      Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland.
FAU - Rudaz, Serge
AU  - Rudaz S
AD  - School of pharmaceutical sciences, Geneva University, Rue Michel Servet 1, 1211, 
      Geneva, Switzerland.
AD  - Swiss Center for Applied Human Toxicology (SCAHT), Missionsstrasse 64, 4055, 
      Basel, Switzerland.
FAU - Desmeules, Jules A
AU  - Desmeules JA
AD  - Clinical Pharmacology and Toxicology Service, Geneva University Hospitals, Rue 
      Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland.
AD  - School of pharmaceutical sciences, Geneva University, Rue Michel Servet 1, 1211, 
      Geneva, Switzerland.
AD  - Swiss Center for Applied Human Toxicology (SCAHT), Missionsstrasse 64, 4055, 
      Basel, Switzerland.
FAU - Daali, Youssef
AU  - Daali Y
AD  - Clinical Pharmacology and Toxicology Service, Geneva University Hospitals, Rue 
      Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland.
AD  - School of pharmaceutical sciences, Geneva University, Rue Michel Servet 1, 1211, 
      Geneva, Switzerland.
AD  - Swiss Center for Applied Human Toxicology (SCAHT), Missionsstrasse 64, 4055, 
      Basel, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20160805
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Cyclosporins)
RN  - GLH0314RVC (Ticagrelor)
RN  - K72T3FS567 (Adenosine)
RN  - Q7ZP55KF3X (valspodar)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & 
      inhibitors/*metabolism
MH  - Adenosine/*analogs & derivatives/metabolism/pharmacology
MH  - Biological Transport, Active/physiology
MH  - Caco-2 Cells
MH  - Cell Line, Tumor
MH  - Cyclosporins/pharmacology
MH  - Humans
MH  - Intestinal Mucosa/*metabolism
MH  - Permeability
MH  - Protein Transport/physiology
MH  - Ticagrelor
OTO - NOTNLM
OT  - Caco-2 cell
OT  - P-glycoprotein
OT  - absorption
OT  - intestinal permeability
OT  - ticagrelor
OT  - transport
EDAT- 2016/07/15 06:00
MHDA- 2017/03/30 06:00
CRDT- 2016/07/15 06:00
PHST- 2016/04/28 00:00 [received]
PHST- 2016/06/29 00:00 [revised]
PHST- 2016/07/08 00:00 [accepted]
PHST- 2016/07/15 06:00 [pubmed]
PHST- 2017/03/30 06:00 [medline]
PHST- 2016/07/15 06:00 [entrez]
AID - 10.1111/fcp.12219 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2016 Dec;30(6):577-584. doi: 10.1111/fcp.12219. Epub 2016 
      Aug 5.