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Titolo:
Facilitated uptake of fentanyl, but not alfentanil, by human pulmonary endothelial cells
Autore:
Waters, CM; Krejcie, TC; Avram, MJ;
Indirizzi:
Northwestern Univ, Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 Anesthesiol, Chicago, IL 60611 USA
Titolo Testata:
ANESTHESIOLOGY
fascicolo: 3, volume: 93, anno: 2000,
pagine: 825 - 831
SICI:
0003-3022(200009)93:3<825:FUOFBN>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLOOD-BRAIN-BARRIER; P-GLYCOPROTEIN; HUMAN-LUNG; INTERINDIVIDUAL VARIABILITY; MULTIDRUG RESISTANCE; CYTOCHROME-P450 3A4; TISSUE DISTRIBUTION; DRUG-INTERACTIONS; PASS UPTAKE; METABOLISM;
Keywords:
antipyrine; facilitated drug uptake; P-glycoprotein blocking antibody;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Avram, MJ Northwestern Univ, Sch Med, Dept Anesthesiol, 303 E Chicago Ave,CH-W139, Chicago, IL 60611 USA Northwestern Univ 303 E Chicago Ave,CH-W139 Chicago IL USA 60611
Citazione:
C.M. Waters et al., "Facilitated uptake of fentanyl, but not alfentanil, by human pulmonary endothelial cells", ANESTHESIOL, 93(3), 2000, pp. 825-831

Abstract

Background: Extensive pulmonary uptake of lipophilic basic amines, such asfentanyl, attenuates early blood drug concentrations after rapid intravenous administration. The basis of this phenomenon is poorly understood. The authors tested the hypothesis that fentanyl uptake into cultured human lung microvascular endothelial (HMVE-L) cells occurs by facilitated uptake in addition to passive diffusion. The authors compared fentanyl and alfentanil uptake with that of antipyrine, a diffusible marker of pulmonary tissue water. In addition, the authors determined the effect of verapamil, a nonspecific inhibitor of drug transport, and UIC2, a blocking antibody of the P-glycoprotein drug transporter, on the uptake of these drugs. Methods: Human lung microvascular endothelial cells were incubated, with varying concentrations of antipyrine and fentanyl or alfentanil in the absence or presence of varying verapamil concentrations or of UIC2. Supernatantswere collected and cells were rinsed and dissolved. Supernatant and fell-associated antipyrine, fentanyl, and alfentanil concentrations were measured. The data were fit to a model of cellular uptake that allowed for passive diffusion and facilitated uptake. Results: Alfentanil uptake by HMVE-L cells was indistinguishable from thatof antipyrine for the concentration ranges studied. In contrast, at low concentrations, fentanyl sequestration into HMVE-L cells was substantially greater than that of antipyrine. Facilitated fentanyl uptake was blocked by verapamil, but not by UIC2, In a concentration-dependent manner. Conclusions: The differential HMVE-L uptake of fentanyl and alfentanil is consistent with the observed differences in the pulmonary uptake of these drugs. This suggests that specific fentanyl uptake and sequestration by HMVE-L cells may be the mechanisms of its extensive pulmonary uptake.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/02/20 alle ore 17:20:51