Variants in the SLCO1B3 gene: interethnic distribution and association with paclitaxel pharmacokinetics

Clin Pharmacol Ther. 2007 Jan;81(1):76-82. doi: 10.1038/sj.clpt.6100011.

Abstract

To explore retrospectively the relationships between paclitaxel pharmacokinetics and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP)1B3. Accumulation of [(3)H]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP. The 334T>G (Ser112Ala), 699G>A (Met233Ile), and 1564G>T (Gly522Cys) loci of SLCO1B3 were screened in 475 individuals from five ethnic groups and 90 European Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of transporting paclitaxel to a significant extent (P=0.003). The 334T>G and 699G>A SNPs were less common in the African-American and Ghanaian populations (P<0.000001). Paclitaxel pharmacokinetics were not associated with the studied SNPs or haplotypes (P>0.3). The studied SNPs in SLCO1B3 appear to play a limited role in the disposition of paclitaxel, although their clinical significance in other ethnic populations remains to be investigated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Continental Population Groups*
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • In Vitro Techniques
  • Oocytes
  • Organic Anion Transporters, Sodium-Independent / genetics*
  • Paclitaxel / pharmacokinetics*
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Xenopus laevis

Substances

  • Antineoplastic Agents, Phytogenic
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Paclitaxel