Variants in the SLCO1B3 Gene: Interethnic Distribution and Association with Paclitaxel Pharmacokinetics
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 [3H]paclitaxel was studied in Xenopus laevis oocytes...
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Veröffentlicht in: | Clinical pharmacology and therapeutics 2007-01, Vol.81 (1), p.76-82 |
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Sprache: | eng |
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Zusammenfassung: | 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 [3H]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 (P0.3). 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.
Clinical Pharmacology & Therapeutics (2007) 81, 76–82. doi:10.1038/sj.clpt.6100011 |
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ISSN: | 0009-9236 1532-6535 |
DOI: | 10.1038/sj.clpt.6100011 |