Journal
CANCER BIOLOGY & THERAPY
Volume 4, Issue 6, Pages 650-653Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.4.6.1731
Keywords
topotecan; ABCG2; pharmacokinetics; pharmacogenetics; accumulation; mutant; in vitro
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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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