ABCMdb

PMID: 23007012

Oh ES, Kim CO, Cho SK, Park MS, Chung JY
Impact of ABCC2, ABCG2 and SLCO1B1 polymorphisms on the pharmacokinetics of pitavastatin in humans.
Drug Metab Pharmacokinet. 2012 Sep 25., [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCC2 p.Cys1446Gly In heterozygotes for ABCC2 C1446G (n=3), systemic exposure and peak plasma concentration (Cmax) of pravastatin were lower than in wild-type homozygotes (CC, n=35) as a consequence of increased MRP2 mRNA expression.18) However, the variation of this allele is synonymous and has been only reported in one small Caucasian population. Login to comment 100 ABCB1 p.Gly1249Ala The insignificant results of G1249A, C3972T, and G1549A associated with pitavastatin PK could be introduced by the same reason. Login to comment 106 ABCB1 p.Gly1249Ala ABCB1 p.Gly1249Ala The C-24T polymorphism is located in the 5`-untranslated region (UTR),36) but this variant combined with the G1549A decreased MRP2 promoter activity by 39% in a functional molecular study.20) In a recent report, the genetic variants C-24T, G1249A, and C3972T appeared to influence transport capacity as a haplotype,37) and C3972T is highly linked with C-24T in all ethnic populations.6) Even though G1249A, C3927T, and G1549A did not influence the PK of pitavastatin in our results (Table1), 1249AA group showed about 2.5-fold higher Cmax and systemic exposure compared to the GG or GA. Login to comment