Influence of sequential exposure to R-verapamil or B8509-035 on rhodamine 123 accumulation in human lymphoblastoid cell lines.
Cancer Chemother Pharmacol
; 32(2): 151-5, 1993.
Article
em En
| MEDLINE
| ID: mdl-8097969
ABSTRACT
Modulators for the reversal of multidrug resistance such as R-verapamil and B8509-035, a dihydropyridine, effectively overcome multidrug resistance in vitro and are currently undergoing clinical trial. One problem with their use is the application protocol; the question as to whether they should be given by continuous administration or in sequential doses in combination with the cytotoxic drugs has to be addressed. Therefore, we examined the influence of the exposure time and the sequence of modulator administration on the active transport of the fluorescent dye rhodamine 123 (R123), a substrate for the P-glycoprotein, in the resistant lymphoblastoid cell line VCR1000 and the parental nonresistant cell line CCRF-CEM. Our results demonstrate the importance of coadministration of R-verapamil and the cytotoxic agent for the modulation of multidrug resistance, whereas the exposure sequence does not seem to be such an essential parameter in the case of B8509-035. This observation should be considered for the further design of clinical studies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rodaminas
/
Di-Hidropiridinas
/
Verapamil
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antineoplásicos
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article