Relative contribution of absorptive and secretory transporters to the intestinal absorption of fexofenadine in rats

被引:10
|
作者
Ujie, Kaori [1 ]
Oda, Masako [1 ]
Kobayashi, Michiya [1 ]
Saitoh, Hiroshi [1 ]
机构
[1] Hlth Sci Univ Hokkaido, Fac Pharmaceut Sci, Dept Pharmaceut, Ishikari, Hokkaido 0610293, Japan
关键词
fexofenadine; intestinal absorption; P-glycoprotein; intestinal secretion; rats;
D O I
10.1016/j.ijpharm.2008.05.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
It has been shown that fexofenadine, a selective non-sedating histamine Hi-receptor antagonist, is a substrate for P-glycoprotein (P-gp) and an organic anion transporting peptide (OATP). This study was undertaken to investigate the relative contribution of these absorptive and secretory transporters to the intestinal absorption of fexofenadine in rats. When 0.1 mM fexofenadine was introduced into duodenal, jejunal, and ileal loops, its disappearance was around 10% over 30 min. Cyclosporine A, but not ketoconazole, probenecid or mitoxantron, significantly increased fexofenadine disappearance in the ileal loops. The serosal-to-mucosal permeation of fexofenadine across the rat ileal segments was approximately 18-fold greater than its mucosal-to-serosal permeation. The secretory orientation of the ileal permeation of fexofenadine was weakened significantly in the presence of cyclosporine A, moderately in the presence of ketoconazole, but was unchanged in the presence of probenecid. When fexofenadine (0.1 or 0.5 mM) was administered to rats intraluminally, plasma concentrations increased linearly up to 120 min. The magnitude of the increase in plasma fexofenadine concentrations in the presence of cyclosporine A was more remarkable at 0.5 mM than at 0.1 mM. The results obtained in this study suggest that the intestinal absorption of fexofenadine is relatively small in rats even if OATP functions as an absorptive transporter for fexofenadine. Low absorption of fexofenadine in rats is attributed to potent secretory transport mediated by P-gp. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:7 / 11
页数:5
相关论文
共 50 条
  • [21] Intestinal sterol transporters and cholesterol absorption inhibition
    Davis, Harry R., Jr.
    Tershakovec, Andrew M.
    Tomassini, Joanne E.
    Musliner, Thomas
    CURRENT OPINION IN LIPIDOLOGY, 2011, 22 (06) : 467 - 478
  • [22] SMALL INTESTINAL ABSORPTIVE FUNCTIONS IN IRON DEFICIENT RATS
    SHARMA, DC
    SINGH, PP
    SIMLOT, MM
    AMERICAN JOURNAL OF DIGESTIVE DISEASES, 1973, 18 (01): : 73 - 74
  • [23] INTESTINAL ABSORPTIVE-CAPACITY IN RATS WITH ETHANOL INGESTION
    DELGADO, MJ
    CARRERAS, O
    RUBIO, JM
    MURILLO, ML
    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1991, 418 (06): : R169 - R169
  • [24] SMALL INTESTINAL ABSORPTIVE FUNCTIONS IN IRON DEFICIENT RATS
    SHARMA, DC
    SIMLOT, MM
    SINGH, PP
    AMERICAN JOURNAL OF DIGESTIVE DISEASES, 1972, 17 (07): : 668 - &
  • [25] Effects of fatty acid glycerol esters on intestinal absorptive and secretory transport of ceftibuten
    Koga, K
    Murakami, M
    Kawashima, S
    BIOLOGICAL & PHARMACEUTICAL BULLETIN, 1999, 22 (04) : 402 - 406
  • [26] Fluoroquinolone disposition: identification of the contribution of renal secretory and reabsorptive drug transporters
    Mulgaonkar, Aditi
    Venitz, Jurgen
    Sweet, Douglas H.
    EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2012, 8 (05) : 553 - 569
  • [27] Targeting Intestinal Transporters for Optimizing Oral Drug Absorption
    Varma, Manthena V.
    Ambler, Catherine M.
    Ullah, Mohammad
    Rotter, Charles J.
    Sun, Hao
    Litchfield, John
    Fenner, Katherine S.
    El-Kattan, Ayman F.
    CURRENT DRUG METABOLISM, 2010, 11 (09) : 730 - 742
  • [28] Significance of intestinal drug efflux transporters for oral absorption
    Warhurst, G.
    JOURNAL OF PHARMACY AND PHARMACOLOGY, 2005, 57 : S116 - S117
  • [29] Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters
    Chen, Lihong
    Tuo, Biguang
    Dong, Hui
    NUTRIENTS, 2016, 8 (01):
  • [30] INTESTINAL LYMPH CHOLESTEROL IN RATS - CONTRIBUTION FROM ABSORPTION, MUCOSAL SYNTHESIS, AND PLASMA TRANSUDATION
    STECHHAHN, K
    SIPAHI, AM
    CASTILHO, LN
    OLIVEIRA, HC
    GOLDBERG, ACK
    CLINICAL RESEARCH, 1984, 32 (02): : A409 - A409