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Titolo:
Commercial taxane formulations induce stomatocytosis and increase blood viscosity
Autore:
Mark, M; Walter, R; Meredith, DO; Reinhart, WH;
Indirizzi:
Kantonsspital, Dept Internal Med, CH-7000 Chur, Switzerland KantonsspitalChur Switzerland CH-7000 al Med, CH-7000 Chur, Switzerland Univ Zurich Hosp, Dept Internal Med, Clin B, Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland al Med, Clin B, Zurich, Switzerland AO ASIF Res Inst, Davos, Switzerland AO ASIF Res Inst Davos SwitzerlandAO ASIF Res Inst, Davos, Switzerland
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 6, volume: 134, anno: 2001,
pagine: 1207 - 1214
SICI:
0007-1188(200111)134:6<1207:CTFISA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-ERYTHROCYTES; CREMOPHOR-EL; CELL-SHAPE; TAXOL; ECHINOCYTOSIS; CYCLOSPORINE; PACLITAXEL; RHEOLOGY;
Keywords:
blood theology; blood viscosity; cardiovascular side effect; erythrocyte shape; taxanes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Walter, R Kantonsspital, Dept Internal Med, CH-7000 Chur, Switzerland Kantonsspital Chur Switzerland CH-7000 -7000 Chur, Switzerland
Citazione:
M. Mark et al., "Commercial taxane formulations induce stomatocytosis and increase blood viscosity", BR J PHARM, 134(6), 2001, pp. 1207-1214

Abstract

1 Taxanes are antineoplastic drugs which have cardiovascular side effects of unknown mechanism. We investigated their influence on blood viscosity and erythrocyte morphology.2 Whole blood was incubated in vitro with increasing concentrations of Taxol (R), Taxotere (R), paclitaxel (0-100 mum)and the vehicles Cremophor-EL and Tween 80 (0-5% vol) for 1 h at 37 degreesC. Plasma and whole blood viscosity (Haematocrit 45%) were measured and erythrocyte morphology was assessed on glutaraldehyde-fixed cells. The same investigations were performed in seven patients before and after a Taxol (R) -infusion.3 Taxol (R) and Taxotere (R) induced a dose- and time-dependent stomatocytic shape transformation of erythrocytes. Paclitaxel alone had no effect, but the vehicles cremophor-EL and Tween 80, used in Taxol (R) and Taxotere (R), respectively, induced a comparable degree of stomatocytosis. This suggests a preferential intercalation of these substances into the inner hemileaflet of the membrane lipid bilayer. Associated with this shape change a dose-dependent increase in plasma and whole blood viscosity was observed. Neither shape nor viscosity changes were reversible upon removal of the agents. After the infusion of 130-300 mg Taxol (R) in patients a slight shift towards stomatocytosis and an increase in whole blood viscosity at high shear rate from 5.09 +/-0.30 to 5.44 +/-0.38 mPa.s (P <0.05) were confirmed.4 Commercial taxane drug formulations induce stomatocytosis and increase blood viscosity, which is due to their formulation vehicles. These findings may contribute to the understanding of the cardiovascular side effects of these drugs.

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Documento generato il 18/01/21 alle ore 15:35:05