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Disposition of atorvastatin, rosuvastatin, and simvastatin in oatp1b2-/- mice and intraindividual variability in human subjects.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2012 Nov; Vol. 52 (11), pp. 1689-97. Date of Electronic Publication: 2011 Dec 13. - Publication Year :
- 2012
-
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.
- Subjects :
- Adult
Animals
Area Under Curve
Atorvastatin
Cross-Over Studies
Female
Fluorobenzenes blood
Heptanoic Acids blood
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors blood
Liver metabolism
Liver-Specific Organic Anion Transporter 1
Male
Mice
Mice, Knockout
Middle Aged
Organic Anion Transporters, Sodium-Independent genetics
Pyrimidines blood
Pyrroles blood
Rosuvastatin Calcium
Simvastatin blood
Sulfonamides blood
Young Adult
Fluorobenzenes pharmacokinetics
Heptanoic Acids pharmacokinetics
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacokinetics
Organic Anion Transporters, Sodium-Independent metabolism
Pyrimidines pharmacokinetics
Pyrroles pharmacokinetics
Simvastatin pharmacokinetics
Sulfonamides pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 52
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 22167570
- Full Text :
- https://doi.org/10.1177/0091270011422815