Effect of ABCG2 genotype on the oral bioavailability of topotecan

Alex Sparreboom, Walter J. Loos*, Herman Burger, Tristan M. Sissung, Jaap Verweij, William D. Figg, Kees Nooter, Hans Gelderblom

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


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.

Original languageEnglish
Pages (from-to)e7-e10
JournalCancer Biology and Therapy
Issue number6
StatePublished - Jun 2005
Externally publishedYes


  • ABCG2
  • Accumulation
  • In vitro
  • Mutant
  • Pharmacogenetics
  • Pharmacokinetics
  • Topotecan


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