ABCMdb

PMID: 18762709

Maeda K, Sugiyama Y
Impact of genetic polymorphisms of transporters on the pharmacokinetic, pharmacodynamic and toxicological properties of anionic drugs.
Drug Metab Pharmacokinet. 2008;23(4):223-35., [PubMed]

Sentences

No. Mutations Sentence Comment

107 ABCG2 p.Gln141Lys The most important SNP in BCRP is C421A (Gln141Lys), which is located at the N-terminus domain (Fig. 5). Login to comment 124 ABCC2 p.Gly699Ala T334G (Ser112Ala) and G669A (Met233Ile) are observed frequently in OATP1B3 gene in all ethnic populations, and these two SNPs are tightly linked to each other.23) T334G mutation in OATP1B3 was reported to increase in the plasma AUC (6-12 hr after oral administration) of mycophenolic acid, suggesting that this mutation decreased the transport function of OATP1B3.62) However, the 1/Tmax value in the erythromycin breath test was significantly higher in subjects with T334G, indicating that T334G accelerates the metabolism of erythromycin, which is inconsistent with the clinical study mentioned above.63) On the other hand, T334G and G699A in OATP1B3 did not affect the pharmacokinetics of paclitaxel, docetaxel, telmisartan, which are substrates of OATP1B3.64-66) Very recently, Kiyotani et al. have shown that SNPs in the non-coding region of OATP1B3 and MRP2 are associated with the frequency of docetaxel-induced severe neutropenia in cancer patients with the use of a data-mining approach from ``Biobank Japan'' (http://www.biobankjp.org/), which possesses genome and serum samples from more than 200,000 patients with clinical information.67) This novel approach enables genome-wide searches to find the unknown causal genes for the modification of drug responses. Login to comment