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Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin.
Clin Pharmacol Ther. 2007 Dec; 82(6):726-33.CP

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.

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Authors+Show Affiliations

Pasanen MK
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Fredrikson H
No affiliation info available
Neuvonen PJ
No affiliation info available
Niemi M
No affiliation info available

MeSH

Administration, OralAdultArea Under CurveAtorvastatinEuropean Continental Ancestry GroupFemaleFluorobenzenesGenotypeHeptanoic AcidsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLiverLiver-Specific Organic Anion Transporter 1MaleOrganic Anion TransportersPolymorphism, GeneticProspective StudiesPyrimidinesPyrrolesReference ValuesRosuvastatin CalciumSulfonamides

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17473846

Citation

Pasanen, M K., et al. "Different Effects of SLCO1B1 Polymorphism On the Pharmacokinetics of Atorvastatin and Rosuvastatin." Clinical Pharmacology and Therapeutics, vol. 82, no. 6, 2007, pp. 726-33.
Pasanen MK, Fredrikson H, Neuvonen PJ, et al. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2007;82(6):726-33.
Pasanen, M. K., Fredrikson, H., Neuvonen, P. J., & Niemi, M. (2007). Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. Clinical Pharmacology and Therapeutics, 82(6), 726-33.
Pasanen MK, et al. Different Effects of SLCO1B1 Polymorphism On the Pharmacokinetics of Atorvastatin and Rosuvastatin. Clin Pharmacol Ther. 2007;82(6):726-33. PubMed PMID: 17473846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin. AU - Pasanen,M K, AU - Fredrikson,H, AU - Neuvonen,P J, AU - Niemi,M, Y1 - 2007/05/02/ PY - 2007/5/3/pubmed PY - 2007/12/7/medline PY - 2007/5/3/entrez SP - 726 EP - 33 JF - Clinical pharmacology and therapeutics JO - Clin Pharmacol Ther VL - 82 IS - 6 N2 - 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. SN - 1532-6535 UR - https://www.unboundmedicine.com/medline/citation/17473846/Different_effects_of_SLCO1B1_polymorphism_on_the_pharmacokinetics_of_atorvastatin_and_rosuvastatin_ L2 - https://doi.org/10.1038/sj.clpt.6100220 DB - PRIME DP - Unbound Medicine ER -