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

Authors
  • Smith, N F
  • Marsh, S
  • Scott-Horton, T J
  • Hamada, A
  • Mielke, S
  • Mross, K
  • Figg, W D
  • Verweij, J
  • McLeod, H L
  • Sparreboom, A
Type
Published Article
Journal
Clinical pharmacology and therapeutics
Publication Date
Jan 01, 2007
Volume
81
Issue
1
Pages
76–82
Identifiers
PMID: 17186002
Source
Medline
License
Unknown

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.

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