CYP2C9*3(1075A > C), ABCB1 and SLCO1B1 genetic polymorphisms and gender are determinants of inter-subject variability in pitavastatin pharmacokinetics.
Copyright policy )CYP2C9*3(1075A > C), ABCB1 and SLCO1B1 genetic polymorphisms and gender are determinants of inter-subject variability in pitavastatin pharmacokinetics.
A pharmacokinetics study was conducted in 12 Chinese volunteers following a single dose of 1 mg, 2 mg and 4 mg of pitavastatin calcium in an open-label, randomized, three-period crossover design. Plasma concentrations of pitavastatin acid and pitavastatin lactone were determined by a HPLC method. Single-nucleotide polymorphisms (SNPs) in ABCB1, ABCG2, SLCO1B1, CYP2C9 and CYP3A5 were determined by TaqMan (MGB) genotyping assay. An analysis was performed on the relationship between the aforementioned SNPs and dose-normalized (based on 1 mg) area under the plasma concentration-time curve extrapolated to infinity [AUC(0-infinity)] and peak plasma concentration (Cmax) values of the acid and lactone forms of pitavastatin. Pitavastatin exhibited linear pharmacokinetics and great inter-subject variability. Compared to CYP2C9*1/*1 carriers, CYP2C9*1/*3 carriers had higher AUC(0-infinity) and Cmax of pitavastatin acid and AUC(0-infinity) of pitavastatin lactone (P C and g.11187G > A on pharmacokinetics of the acid and lactone forms were observed. Compared to non-SLCO1B1*17 carriers, SLCO1B1*17 carriers had higher Cmax and AUC(0-infinity) of the acid and lactone forms (P A, c.421C > A, SLCO1B1 c.388A>G, c.571T>C and c.597C>T. We conclude that CYP2C9*3, ABCB1 G2677T/A, SLCO1B1 c.521T>C, SLCO1B1 g.11187G > A, SLCO1B1*17 and gender contribute to inter-subject variability in pitavastatin pharmacokinetics. Personalized medicine should be necessary for hypercholesterolaemic patients receiving pitavastatin.
- Zhejiang Ocean University China (People's Republic of)
Adult, Male, ATP Binding Cassette Transporter, Subfamily B, Cross-Over Studies, Genotype, Liver-Specific Organic Anion Transporter 1, Organic Anion Transporters, DNA, Polymerase Chain Reaction, Lactones, Asian People, Haplotypes, Area Under Curve, Humans, Female, ATP Binding Cassette Transporter, Subfamily B, Member 1, Aryl Hydrocarbon Hydroxylases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cytochrome P-450 CYP2C9, Half-Life
Adult, Male, ATP Binding Cassette Transporter, Subfamily B, Cross-Over Studies, Genotype, Liver-Specific Organic Anion Transporter 1, Organic Anion Transporters, DNA, Polymerase Chain Reaction, Lactones, Asian People, Haplotypes, Area Under Curve, Humans, Female, ATP Binding Cassette Transporter, Subfamily B, Member 1, Aryl Hydrocarbon Hydroxylases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cytochrome P-450 CYP2C9, Half-Life
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