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Research Paper
Effect of ABCG2 Genotype on the Oral Vioavailability of Topotecan
Alex Sparreboom, Walter J. Loos, Herman Burger, Tristan M. Sissung, Jaap Verweij, William D. Figg, Kees Nooter and Hans Gelderblom
volume 4 | issue 6
june 2006Pages: 650-653
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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 non-synonymous 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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.