Abstract
Response to statin therapy is often unpredictable because of variability in metabolism and transport. In the recently created organic anion transporting-polypeptide 1b2 (Oatp1b2/Slco1b2)-null mice, the investigators found significantly lower liver-to-plasma ratios compared with controls for atorvastatin (16.0 ± 5.1 vs 43.5 ± 13.7, P = .002) and rosuvastatin (15.2 ± 3.3 vs 28.4 ± 9.3, P = .03), but not simvastatin (5.2 ± 1.1 vs 6.3 ± 2.9, P = .49), following tail vein injection of 1 mg/kg of each drug. In addition, the investigators examined intraindividual variation in atorvastatin, rosuvastatin, and simvastatin pharmacokinetics in healthy human subjects in a crossover study design. Areas under the plasma concentration-time curve of atorvastatin and simvastatin acid were significantly related (Spearman r = 0.68; P = .035), whereas rosuvastatin profile was not related to atorvastatin or simvastatin exposure. Together, these results in mice and humans demonstrate that predictability of exposure to one statin based on another is dependent on the specific statin pairs and the context in which they are compared.
Publication types
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Area Under Curve
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Atorvastatin
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Cross-Over Studies
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Female
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Fluorobenzenes / blood
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Fluorobenzenes / pharmacokinetics*
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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 / 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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Mice
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Mice, Knockout
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Middle Aged
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Organic Anion Transporters, Sodium-Independent / genetics
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Organic Anion Transporters, Sodium-Independent / metabolism*
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Pyrimidines / blood
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Pyrimidines / pharmacokinetics*
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Pyrroles / blood
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Pyrroles / pharmacokinetics*
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Rosuvastatin Calcium
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Simvastatin / blood
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Simvastatin / pharmacokinetics*
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Sulfonamides / blood
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Sulfonamides / pharmacokinetics*
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Young Adult
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, Sodium-Independent
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Pyrimidines
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Pyrroles
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Slco1b2 protein, mouse
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Sulfonamides
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Rosuvastatin Calcium
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Atorvastatin
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Simvastatin