Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: Consequences for pravastatin pharmacokinetics

Nishizato, Yohei; Ieiri, Ichiro; Suzuki, Hiroshi; Kimura, Miyuki; Kawabata, Kiyoshi; Hirota, Tomoyoshi; Takane, Hiroshi; Irie, Shin; Kusuhara, Hiroyuki; Urasaki, Yoko; Urae, Akinori; Higuchi, Shun; Otsubo, Kenji; Sugiyama, Yuichi

doi:10.1016/s0009-9236(03)00060-2

Cited by 480 publications

(439 citation statements)

References 36 publications

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“…Another functionally important SNP is 521T4C (rs4149056; V174A), SNP 524 in block 4. 8 In our study, SNP 524 Polymorphisms of drug transporters in three races S Endo et al Polymorphisms of drug transporters in three races S Endo et al Polymorphisms of drug transporters in three races S Endo et al Polymorphisms of drug transporters in three races S Endo et al was not associated with changes in any pharmacokinetic parameters. In addition to this, the SLCO1B1*1A (388A-521C), *1B (388G-521T), *5 (388A-521C) and *15 (388G-521C) haplotypes, 4 which were formed through these two SNPs, did not show any statistical significant associations (data not shown).…”

Section: Discussionmentioning

confidence: 44%

“…Two aliquots of at least 0.7 ml of plasma each were removed, placed in screw-cap polypropylene tubes and immediately stored at À20 1C or below until the analysis. Blood samples were collected before and at 0.5, 1, 1.5, 2, 3, 4,6,8,12,16,24,36,48,60 and 72 h following each dose. The plasma concentrations of olmesartan were determined by a validated method of high-performance liquid chromatography with fluorescence detection.…”

Section: Sample Treatments and Pharmacokinetic Data Analysismentioning

confidence: 99%

“…[4][5][6][7] Moreover, the 521C/C genotype has been associated with increased plasma concentrations of statins and glinides in human studies. [8][9][10] In SLCO1B3, several single-nucleotide polymorphisms (SNPs) have been identified in coding and noncoding regions. At least three nonsynonymous SNPs have been found so far, with 334T4G (S112A) and 699G4A (M233I) increasing transporter activity in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

et al. 2012

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It has been reported that organic anion-transporting polypeptide (OATP) 1B1, OATP1B3 and multidrug resistance-associated protein 2 are involved in the hepatobiliary transport of olmesartan. We investigated the association of SLCO1B1, SLCO1B3 and ABCC2 polymorphisms with the pharmacokinetics of olmesartan. We sequenced all exons, exon-intron junctions and the 5 0 and 3 0 flanking regions of the three genes in 115 individuals from African-American, Hispanic and Caucasian populations who had participated in our clinical studies. A total of 348 single-nucleotide polymorphisms (SNPs) were identified with a minor allele frequency of X0.01 in at least one population; 132 SNPs were detected in SLCO1B1, 130 in SLCO1B3 and 86 in ABCC2. We characterized the linkage disequilibrium (LD) and haplotypes shared across the populations and then evaluated the association between the haplotypes and the pharmacokinetics of olmesartan. Seven inter-ethnic LD blocks were observed in SLCO1B1, while three in SLCO1B3 and four in ABCC2. Although extensive variability in the sequences of SLCO1B1, SLCO1B3 and ABCC2 existed across the three populations, there was no remarkable difference in any pharmacokinetic parameters of olmesartan between subjects with and without any major haplotypes in the three transporter genes we tested.

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Section: Discussionmentioning

confidence: 44%

Section: Sample Treatments and Pharmacokinetic Data Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

et al. 2012

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“…Mwinyi et al 8 reported that the area under the concentration curve (0-6 h) in SLCO1B1*1a/*5 carriers (n ¼ 10) was 1.4-fold larger than that in SLCO1B1*1a/*1a carriers (n ¼ 10). Nishizato et al 6 reported that nonrenal clearances of pravastatin in SLCO1B1*1b/*15 carriers (n ¼ 9) and in SLCO1B1*15/*15 carriers (n ¼ 1) were 55 and 13%, respectively, of that in SLCO1B1*1b/*1b carriers (n ¼ 4). Therefore, although the Cell-surface biotinylation analysis was performed and OATP1B1 variants were detected by western blotting.…”

Section: T Furihata Et Almentioning

confidence: 99%

Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy

et al. 2009

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In the present study, we analyzed the function of a novel mutation (c.1628T4G, p.Leu543Trp) in the solute carrier organic anion transporter (SLCO) 1B1 gene, encoding organic anion transporting polypeptide (OATP) 1B1, which was identified in a patient with pravastatin-induced myopathy. OATP1B1 variants carrying the mutation (OATP1B1*1a þ c.1628T4G or *1b þ c.1628T4G) showed a reduced transporting activity toward typical substrates and pravastatin compared with the activity of the references (OATP1B1*1a or *1b). This was due to reduction in V max values of the variants, not due to change in their K m values. OATP1B1*1b þ c.1628T4G was normally expressed on the plasma membrane of HEK293 cells at the same level as that of OATP1B1*1b. Taken together, our results suggest that the mutation c.1628T4G (p.Leu543Trp) reduced the function of OATP1B1 probably due to decrease in turnover rate of one OATP1B1 molecule rather than impairment of protein sorting to the plasma membrane.

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“…Several single-nucleotide polymorphisms (SNPs) have been identified in SLCO1B1 (Nozawa et al 2002;Tirona et al 2001), and some are reported to be associated with alterations in the pharmacokinetics of certain substrate drugs, including repaglinide (Niemi et al 2005a), fexofenadine (Niemi et al 2005b), pitavastatin (Chung et al 2005;Ieiri et al 2007), and pravastatin (Mwinyi et al 2004;Niemi et al 2004;Nishizato et al 2003). Particularly subjects having SLCO1B1*15 allele (possessing both 388A [G and 521T[C) showed elevated systemic exposure of pravastatin as compared to subjects without this allele (Niemi et al 2004;Nishizato et al 2003). In contrast, some reports indicated that SLCO1B1*1b allele (possessing 388A [G) showed enhanced transport activity of OATP1B1 as compared with wild-type allele (i.e., *1a allele) (Maeda et al 2006;Mwinyi et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism

et al. 2008

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The impact of SLCO1B1 polymorphism on the pharmacokinetics of olmesartan and on the pharmacokinetic interaction between pravastatin and olmesartan was investigated. On day 1, ten healthy volunteers took an oral dose (10 mg) of pravastatin. After a 3-day washout period, each subject received olmesartan medoxomil (10 mg) for 3 days. On day 8, they received olmesartan medoxomil (10 mg) and pravastatin (10 mg) concurrently, and pharmacokinetic profiles were compared with those in each single-dose phase with regard to the SLCO1B1 genotypes (*1b/*1b, *1b/*15, and *15/*15). In the single-dose phase, the mean C max and AUC 0-24 of olmesartan tended to be higher in *15/*15 subjects than in *1b/*1b subjects, while the mean CL t /F (±SD) in *15/*15 subjects was significantly lower than that in *1b/*1b subjects. No statistically significant differences were observed in any pharmacokinetic parameters between single-dose and co-administration phases for both pravastatin and RMS-416. These results suggest that OATP1B1 plays a role in the pharmacokinetics of olmesartan, and the co-administration of olmesartan does not affect the pharmacokinetics of pravastatin or its metabolite, RMS-416, although larger scale clinical studies are needed to confirm these observations due to the small sample size in the present study.

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Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: Consequences for pravastatin pharmacokinetics

Abstract: Certain commonly occurring single-nucleotide polymorphisms in OATP-C, such as T521C (Val174Ala), are likely to be associated with altered pharmacokinetics of pravastatin. Large clinical studies are needed to confirm these observations.

Cited by 480 publications

References 36 publications

Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy

Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism

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