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Titolo:
P-glycoprotein inhibition leads to enhanced disruptive effects by anti-microtubule cytostatics at the in vitro blood-brain barrier
Autore:
van der Sandt, ICJ; Gaillard, PJ; Voorwinden, HH; de Boer, AG; Breimer, DD;
Indirizzi:
Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Pharmacol, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 5, volume: 18, anno: 2001,
pagine: 587 - 592
SICI:
0724-8741(200105)18:5<587:PILTED>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTIDRUG-RESISTANCE; ORAL ABSORPTION; PHARMACOKINETICS; INFUSION; DRUG; PERMEABILITY; COLCHICINE; DYNAMICS;
Keywords:
P-glycoprotein; blood-brain barrier; anti-microtubule drugs; in vitro; Pgp modulators;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: van der Sandt, ICJ Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Pharmacol, POB 9503, NL-2300 RA Leiden, Netherlands Leiden Univ POB 9503 Leiden Netherlands NL-2300 RA nds
Citazione:
I.C.J. van der Sandt et al., "P-glycoprotein inhibition leads to enhanced disruptive effects by anti-microtubule cytostatics at the in vitro blood-brain barrier", PHARM RES, 18(5), 2001, pp. 587-592

Abstract

Purpose. To investigate whether P-glycoprotein (Pgp) protects the in vitroBBB against the cytotoxic effects of anti-tumour drugs. Methods. In an in vitro BBB coculture model the influence of the anti-microtubule drugs vinblastine. colchicine, paclitaxel and the non-antimicrotubule drugs doxorubicin, fluorouracil and etoposide in the absence or presenceof Pgp modulators on the trans-endothelial electrical resistance (TEER), which is an indicator for the integrity, was investigated. Results. In the absence of Pgp modulators vinblastine, colchicine and paclitaxel dose dependently decreased TEER values to less than 20% of control. Non-anti-microtubule drugs did not affect TEER values. Following competitive inhibition of Pgp by various Pgp modulators and substrates, even low concentrations of vinblastine, colchicine and paclitaxel substantially decreased TEER. IC50 values of LY 335979, SDZ-PSC 833, cyclosporin A, and verapamilwere 0.03, 0.25, 0.16. and 13.7 muM, respectively. Conclusions. These results indicate that Pgp normally protects the in vitro BBB against the disruptive effects of anti-microtubule drugs. but its integrity is lost when anti-microtubule drugs are used in combination with potent Pgp modulators. In addition, this procedure offers the possibility to characterize Pgp modulators and substrates with respect to their efficacy and to elucidate drug interactions at the level of Pgp.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:42:47