Effect of ABCG2 genotype on the oral bioavailability of topotecan.
Cancer Biol Ther
; 4(6): 650-8, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15908806
ABSTRACT
ABCG2 (BCRP/MXR/ABCP) functions as an efflux transporter for many agents, including topotecan, and the protein is expressed at high levels in the human intestine. Some individuals possess a nonsynonymous variant in the ABCG2 gene at nucleotide 421, substituting lysine for glutamine on position 141 at exon 5. The present pilot study indicates that this genotype results in a 30% reduced efflux transport of topotecan in vitro compared to the wild-type. In a preliminary fashion, the heterozygous CA allele observed in two patients was associated with a 1.34-fold increased oral bioavailability of topotecan compared to the bioavailability in ten patients with the wild-type allele (42.0% versus 31.4%; p = 0.037). It is suggested that the high frequency of the A allele in certain ethnic groups may have therapeutic implications for individuals treated with topotecan or other ABCG2 substrates.
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Carcinoma de Células Pequenas
/
Transportadores de Cassetes de Ligação de ATP
/
Topotecan
/
Proteínas de Neoplasias
/
Antineoplásicos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer Biol Ther
Assunto da revista:
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos