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Pharm Res
2009 Mar 01;263:560-7. doi: 10.1007/s11095-008-9771-4.
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Concentration-dependent effect of naringin on intestinal absorption of beta(1)-adrenoceptor antagonist talinolol mediated by p-glycoprotein and organic anion transporting polypeptide (Oatp).
Shirasaka Y
,
Li Y
,
Shibue Y
,
Kuraoka E
,
Spahn-Langguth H
,
Kato Y
,
Langguth P
,
Tamai I
.
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The purpose of this study is to clarify the impact of P-gp and Oatp on intestinal absorption of the beta(1)-adrenoceptor antagonist talinolol. P-gp-mediated transport was measured in LLC-PK1/MDR1 cells. Oatp-mediated uptake was evaluated with Xenopus oocytes expressing Oatp1a5. Rat intestinal permeability was measured by the in situ closed loop method. In vivo absorption was pharmacokinetically assessed by measuring plasma concentration after oral administration in rats. In LLC-PK1/MDR1 cells, the permeability of talinolol was markedly higher in the secretory direction than in the absorptive one. The uptake of talinolol by Xenopus oocytes expressing Oatp1a5 was significantly increased compared with that by water-injected oocytes. Naringin inhibited talinolol uptake by Oatp1a5 (IC (50) = 12.7 microM). The reported IC (50) value of naringin for P-gp-mediated transport of talinolol is approximately 2,000 microM. Rat intestinal permeability of talinolol was significantly decreased in the presence of 200 microM naringin, but was significantly increased by 2,000 microM naringin. Similar results were obtained in in vivo absorption studies in rats. The absorption behavior of talinolol can be explained by the involvement of both P-gp and Oatp, based on characterization of talinolol transport by Oatp1a5 and P-gp, and the effects of naringin.
Ambudkar,
Biochemical, cellular, and pharmacological aspects of the multidrug transporter.
1999, Pubmed
Ambudkar,
Biochemical, cellular, and pharmacological aspects of the multidrug transporter.
1999,
Pubmed
Augustine,
Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier.
2005,
Pubmed
Bailey,
Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice.
2007,
Pubmed
de Castro,
Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells.
2007,
Pubmed
De Castro,
Variation of flavonoids and furanocoumarins in grapefruit juices: a potential source of variability in grapefruit juice-drug interaction studies.
2006,
Pubmed
Dresser,
Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine.
2002,
Pubmed
Fagerholm,
Regional intestinal permeability in rats of compounds with different physicochemical properties and transport mechanisms.
1997,
Pubmed
Fromm,
P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs.
2000,
Pubmed
Hanafy,
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.
2001,
Pubmed
Hilgendorf,
Selective downregulation of the MDR1 gene product in Caco-2 cells by stable transfection to prove its relevance in secretory drug transport.
2005,
Pubmed
Kikuchi,
Transporter-mediated intestinal absorption of fexofenadine in rats.
2006,
Pubmed
,
Xenbase
Kobayashi,
Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane.
2003,
Pubmed
Koitabashi,
Orange juice increased the bioavailability of pravastatin, 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, in rats and healthy human subjects.
2006,
Pubmed
Macheras,
Gastrointestinal drug absorption: is it time to consider heterogeneity as well as homogeneity?
1997,
Pubmed
Maeda,
Identification of influx transporter for the quinolone antibacterial agent levofloxacin.
2007,
Pubmed
,
Xenbase
Masaoka,
Site of drug absorption after oral administration: assessment of membrane permeability and luminal concentration of drugs in each segment of gastrointestinal tract.
2006,
Pubmed
Naruhashi,
Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein.
2001,
Pubmed
Nozawa,
Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human.
2004,
Pubmed
Ofer,
Bidirectional membrane transport: simulations of transport inhibition in uptake studies explain data obtained with flavonoids.
2006,
Pubmed
Schinkel,
P-Glycoprotein, a gatekeeper in the blood-brain barrier.
1999,
Pubmed
Schwarz,
Grapefruit juice ingestion significantly reduces talinolol bioavailability.
2005,
Pubmed
Schwarz,
Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans.
1999,
Pubmed
Schwarz,
P-glycoprotein inhibitor erythromycin increases oral bioavailability of talinolol in humans.
2000,
Pubmed
Shirasaka,
Effect of P-glycoprotein expression levels on the concentration-dependent permeability of drugs to the cell membrane.
2008,
Pubmed
Shirasaka,
Scaling of in vitro membrane permeability to predict P-glycoprotein-mediated drug absorption in vivo.
2008,
Pubmed
Shitara,
Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport.
2002,
Pubmed
Spahn-Langguth,
P-glycoprotein transporters and the gastrointestinal tract: evaluation of the potential in vivo relevance of in vitro data employing talinolol as model compound.
1998,
Pubmed
Spahn-Langguth,
Grapefruit juice enhances intestinal absorption of the P-glycoprotein substrate talinolol.
2001,
Pubmed
Tamai,
Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family.
2000,
Pubmed
Tamai,
Nonlinear intestinal absorption of 5-hydroxytryptamine receptor antagonist caused by absorptive and secretory transporters.
1997,
Pubmed
Tani,
Involvement of organic anion transporting polypeptide 1a5 (Oatp1a5) in the intestinal absorption of endothelin receptor antagonist in rats.
2008,
Pubmed
,
Xenbase
Tanigawara,
Role of P-glycoprotein in drug disposition.
2000,
Pubmed
Tourniaire,
Molecular mechanisms of the naringin low uptake by intestinal Caco-2 cells.
2005,
Pubmed
Trausch,
Disposition and bioavailability of the beta 1-adrenoceptor antagonist talinolol in man.
1995,
Pubmed
Tsuji,
Carrier-mediated intestinal transport of drugs.
1996,
Pubmed
Verschraagen,
P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil.
1999,
Pubmed
Walters,
Expression, transport properties, and chromosomal location of organic anion transporter subtype 3.
2000,
Pubmed
Weitschies,
The talinolol double-peak phenomenon is likely caused by presystemic processing after uptake from gut lumen.
2005,
Pubmed
Westphal,
Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein.
2000,
Pubmed
Wetterich,
Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration- and dose-dependent absorption in vitro and in vivo.
1996,
Pubmed
Yu,
The contribution of P-glycoprotein to pharmacokinetic drug-drug interactions.
1999,
Pubmed
Zhou,
Pharmacokinetic strategies in deciphering atypical drug absorption profiles.
2003,
Pubmed
Zschiesche,
Stereoselective disposition of talinolol in man.
2002,
Pubmed
