Abstract
Thirty-two healthy volunteers with different SLCO1B1 genotypes ingested a 20 mg dose of atorvastatin and 10 mg dose of rosuvastatin with a washout period of 1 week. Subjects with the SLCO1B1 c.521CC genotype (n=4) had a 144% (P<0.001) or 61% (P=0.049) greater mean area under the plasma atorvastatin concentration-time curve from 0 to 48 h (AUC(0-48 h)) than those with the c.521TT (n=16) or c.521TC (n=12) genotype, respectively. The AUC(0-48 h) of 2-hydroxyatorvastatin was 100% greater in subjects with the c.521CC genotype than in those with the c.521TT genotype (P=0.018). Rosuvastatin AUC(0-48 h) and peak plasma concentration (Cmax) were 65% (P=0.002) and 79% (P=0.003) higher in subjects with the c.521CC genotype than in those with the c.521TT genotype. These results indicate that, unexpectedly, SLCO1B1 polymorphism has a larger effect on the AUC of atorvastatin than on the more hydrophilic rosuvastatin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Adult
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Area Under Curve
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Atorvastatin
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Female
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Fluorobenzenes / administration & dosage
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Fluorobenzenes / blood
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Fluorobenzenes / pharmacokinetics*
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Genotype
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Heptanoic Acids / administration & dosage
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Heptanoic Acids / blood
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Heptanoic Acids / pharmacokinetics*
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / blood
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
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Liver / metabolism*
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Liver-Specific Organic Anion Transporter 1
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Male
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Organic Anion Transporters / genetics*
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Organic Anion Transporters / metabolism
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Polymorphism, Genetic*
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Prospective Studies
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Pyrimidines / administration & dosage
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Pyrimidines / blood
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Pyrimidines / pharmacokinetics*
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Pyrroles / administration & dosage
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Pyrroles / blood
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Pyrroles / pharmacokinetics*
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Reference Values
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Rosuvastatin Calcium
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Sulfonamides / administration & dosage
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Sulfonamides / blood
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Sulfonamides / pharmacokinetics*
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White People / genetics
Substances
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Fluorobenzenes
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Heptanoic Acids
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Liver-Specific Organic Anion Transporter 1
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Organic Anion Transporters
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Pyrimidines
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Pyrroles
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SLCO1B1 protein, human
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Sulfonamides
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Rosuvastatin Calcium
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Atorvastatin