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Titolo:
Mechanisms of transport and structure-permeability relationship of sulfasalazine and its analogs in Caco-2 cell monolayers
Autore:
Liang, E; Proudfoot, J; Yazdanian, M;
Indirizzi:
Boehringer Ingelheim Pharmaceut Inc, Dept Pharmaceut, Ridgefield, CT 06877USA Boehringer Ingelheim Pharmaceut Inc Ridgefield CT USA 06877 , CT 06877USA Boehringer Ingelheim Pharmaceut Inc, Dept Med Chem, Ridgefield, CT 06877 USA Boehringer Ingelheim Pharmaceut Inc Ridgefield CT USA 06877 CT 06877 USA
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 10, volume: 17, anno: 2000,
pagine: 1168 - 1174
SICI:
0724-8741(200010)17:10<1168:MOTASR>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC CATION TRANSPORTER; ACTIVE THERAPEUTIC MOIETY; P-GLYCOPROTEIN; 5-AMINOSALICYLIC ACID; MEMBRANE; RAT; EXCHANGE; BRAIN; SULPHASALAZINE; CLONING;
Keywords:
sulfasalazine; Caco-2 cells; structure-permeability relationship; multiple cellular efflux mechanisms;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Yazdanian, M Boehringer Ingelheim Pharmaceut Inc, Dept Pharmaceut, 900 Ridgebury Rd,POB368, Ridgefield, CT 06877 USA Boehringer Ingelheim Pharmaceut Inc 900 Ridgebury Rd,POB 368 Ridgefield CT USA 06877
Citazione:
E. Liang et al., "Mechanisms of transport and structure-permeability relationship of sulfasalazine and its analogs in Caco-2 cell monolayers", PHARM RES, 17(10), 2000, pp. 1168-1174

Abstract

Purpose. To investigate the mechanisms involved in transport of sulfasalazine in Caco-2 cells. Methods. Permeability coefficients of sulfasalazine and its analogs acrossCaco-2 cell monolayers were measured as a function of direction of transport, energy and concentration dependence, and in the presence of inhibitors of various cellular efflux pumps and transporters. Results. Permeability coefficients of sulfasalazine across Caco-2 cell monolayers were approximately 342-, 261-, and 176-ford higher from basolateralto apical direction (BL-->AP) than from apical to basolateral direction (AP-->BL) at 100, 200, and 500 muM, respectively. Carrier permeability coefficient, non-saturable membrane permeability coefficient, and Michaelis constant were estimated to be 1.4x10(-5) cm/s, 1.9x10(-8) cm/s, and 369 muM, respectively. The efflux of sulfasalazine was completely blocked at CC and in the presence of an uncoupler of oxidative phosphorylation. Using cellular egfflux inhibitors, the permeability of sulfasalazine was shown to depend onmultidrug resistance-associated protein and anion sensitive transport mechanisms. Structure-permeability studies showed that the affinity of sulfasalazine for the cellular efflux pumps and transporters in Caco-2 cells depended strongly on the carboxylic acid functional group. Conclusions. The permeability of sulfasalazine across Caco-2 cell monolayer is very low due to its strong interaction with multiple celular efflux pumps and transporters. This may partially explain its low absorption in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 01:49:18