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Disposition of Atorvastatin, Rosuvastatin, and Simvastatin in Oatp1b2‐/‐ Mice and Intraindividual Variability in Human Subjects
Author(s) -
DeGorter M. K.,
Urquhart B. L.,
Gradhand U.,
Tirona R. G.,
Kim R. B.
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011422815
Subject(s) - rosuvastatin , simvastatin , atorvastatin , statin , context (archaeology) , medicine , pharmacokinetics , pharmacology , crossover study , hmg coa reductase , bioavailability , endocrinology , chemistry , placebo , biology , biochemistry , pathology , reductase , enzyme , paleontology , alternative medicine
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.