Dmd054866 520..528
نویسندگان
چکیده
Edoxaban (the free base of DU-176b), an oral direct factor Xa inhibitor, is mainly excreted unchanged into urine and feces. Because active membrane transport processes such as active renal secretion, biliary excretion, and/or intestinal secretion, and the incomplete absorption of edoxaban after oral administration have been observed, the involvement of drug transporters in the disposition of edoxaban was investigated. Using a bidirectional transport assay in human colon adenocarcinoma Caco-2 cell monolayers, we observed the vectorial transport of [C]edoxaban, which was completely inhibited by verapamil, a strong P-glycoprotein (P-gp) inhibitor. In an in vivo study, an increased distribution of edoxaban to the brain was observed in Mdr1a/1b knockout mice when compared with wild-type mice, indicating that edoxaban is a substrate for P-gp. However, there have been no observations of significant transport of edoxaban by renal or hepatic uptake transporters, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, or organic anion transporting polypeptide (OATP)1B1. Edoxaban exhibited no remarkable inhibition of OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, or P-gp up to 30 mM; therefore, the risk of clinical drug–drug interactions due to any edoxaban-related transporter inhibition seems to be negligible. Our results demonstrate that edoxaban is a substrate of P-gp but not of other major uptake transporters tested. Because metabolism is a minor contributor to the total clearance of edoxaban and strong P-gp inhibitors clearly impact edoxaban transport, the P-gp transport system is a key factor for edoxaban’s disposition.
منابع مشابه
Sports Med 2005; 35 (6): 501-536
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 502 1. Physical Demands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503 1.1 Game Intensity . . . . . . . . . . . . . . . . . . . . . . ...
متن کاملIsolation and preliminary characterization of new cytochrome c from autotrophic haloalkaliphilic sulfur-oxidizing bacterium Thioalkalivibrio nitratireducens.
New small cytochrome c (TniCYT) was purified from haloalkaliphilic sulfur-oxidizing bacterium Thioalkalivibrio nitratireducens. The protein was analyzed by mass spectrometry as well as using visible, CD and EPR spectroscopy. It was found that TniCYT is a monomer with a molecular mass of 9461 Da which contains two hemes per molecule. The data of CD and EPR spectroscopy showed that two hemes poss...
متن کاملScenarios for the Cross-comparison of the Link and System Level Simulators
at most three retransmissions. The most important parameters 519 of the test scenarios are listed in Table I. The first scenario 520 (8.2.1.1.1/1) refers to the test scenario described above. The 521 OLSM scenario (8.2.1.3.2/1) utilizes a rank two transmission, 522 that is, transmission of two spatial streams. 523 Simulation results for the considered scenarios are shown 524 in Figure 8. The da...
متن کاملGrowth Characters and Yield of Some Selected Lines of Grass Pea (Lathyrus sativus)
The grass pea (Lathyrus sativus) is a dual purpose forage seed legume crop. It has a good potential as winter forage legume under Saudi Arabian conditions. This study was conducted in 1993/94 and 1994/95 seasons to evaluate 15 selection lines of the Grass Pea for forage, seed yields and other growth characters. Combined analysis of data from the two years revealed significant difference between...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2014