Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males
- PMID: 16784736
- DOI: 10.1016/j.cca.2006.05.010
Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males
Abstract
Background: Rosuvastatin, a novel potent HMG-CoA reductase inhibitor, is excreted into bile mediated by breast cancer resistance protein (BCRP). Our objective was to determine the association between the most frequent single nucleotide polymorphisms (SNPs) of the BCRP (421C>A) and the pharmacokinetics of rosuvastatin.
Method: Pre-screening of SLCO1B1 521TC and CYP2C9*1/*3 were performed before this pharmacokinetic study. Fourteen healthy volunteers who are SLCO1B1 521TT and CYP2C9*1/*1 wild-type homozygotes were selected to participate in this study. Seven were 421CC wild-type of BCRP, the others were carriers with at least one 421C>A mutant allele (five subjects had a genotype of 421CA and two were homozygotes of 421AA). Each was given a single oral dose of 20 mg rosuvastatin. The plasma concentrations of rosuvastatin were measured for up to 72 h by LC-MS.
Results: The pharmacokinetic parameters of rosuvastatin showed a significantly difference between the two genotyped groups. The AUC(0-72) and AUC(0-infinity) of rosuvastatin were lower in the 421CC group than in the 421CA+421AA group (33.8+/-11.4 vs. 59.6+/-22.2 ng.h/ml, P=0.018; 34.9+/-11.9 vs. 62.2+/-23.5 ng.h/ml, P=0.018), respectively. The C(max) value was higher in the 421CA+421AA group than that in the 421CC group (9.9+/-5.4 vs. 5.1+/-2.4 ng/ml, P=0.048). The CL/F value was lower in the 421CA+421AA group than that in the 421CC group (384.7+/-161.2 vs. 674.0+/-297.6 l/h, P=0.043). The T(1/2) and T(max) values showed no difference between these groups.
Conclusions: The BCRP 421C>A polymorphism may play an important role in the pharmacokinetics of rosuvastatin in healthy Chinese males after the exclusion of impact of SLCO1B1 and CYP2C9 genetic polymorphism.
Similar articles
-
Marked Alteration of Rosuvastatin Pharmacokinetics in Healthy Chinese with ABCG2 34G>A and 421C>A Homozygote or Compound Heterozygote.J Pharmacol Exp Ther. 2015 Sep;354(3):310-5. doi: 10.1124/jpet.115.225045. Epub 2015 Jun 16. J Pharmacol Exp Ther. 2015. PMID: 26081159
-
ABCB1 gene polymorphisms, ABCB1 haplotypes and ABCG2 c.421c > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics.Pharmazie. 2013 Feb;68(2):129-34. Pharmazie. 2013. PMID: 23469685 Clinical Trial.
-
Ethnic variability in the plasma exposures of OATP1B1 substrates such as HMG-CoA reductase inhibitors: a kinetic consideration of its mechanism.Clin Pharmacol Ther. 2013 Jul;94(1):37-51. doi: 10.1038/clpt.2012.221. Epub 2012 Nov 7. Clin Pharmacol Ther. 2013. PMID: 23443754 Review.
-
The ABCG2 transporter and its relations with the pharmacokinetics, drug interaction and lipid-lowering effects of statins.Expert Opin Drug Metab Toxicol. 2011 Jan;7(1):49-62. doi: 10.1517/17425255.2011.538383. Epub 2010 Nov 23. Expert Opin Drug Metab Toxicol. 2011. PMID: 21091277 Review.
-
ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin.Clin Pharmacol Ther. 2009 Aug;86(2):197-203. doi: 10.1038/clpt.2009.79. Epub 2009 May 27. Clin Pharmacol Ther. 2009. PMID: 19474787 Clinical Trial.
Cited by
-
Impacts of ABCG2 loss of function variant (p. Gln141Lys, c.421 C > A, rs2231142) on lipid levels and statin efficiency: a systematic review and meta-analysis.BMC Cardiovasc Disord. 2024 Apr 8;24(1):202. doi: 10.1186/s12872-024-03821-2. BMC Cardiovasc Disord. 2024. PMID: 38589776 Free PMC article.
-
Tumor-acquired somatic mutation affects conformation to abolish ABCG2-mediated drug resistance.Drug Resist Updat. 2024 Mar;73:101066. doi: 10.1016/j.drup.2024.101066. Epub 2024 Feb 6. Drug Resist Updat. 2024. PMID: 38387283
-
The Association between ABCG2 421C>A (rs2231142) Polymorphism and Rosuvastatin Pharmacokinetics: A Systematic Review and Meta-Analysis.Pharmaceutics. 2022 Feb 24;14(3):501. doi: 10.3390/pharmaceutics14030501. Pharmaceutics. 2022. PMID: 35335877 Free PMC article. Review.
-
Quantification of CYP3A and Drug Transporters Activity in Healthy Young, Healthy Elderly and Chronic Kidney Disease Elderly Patients by a Microdose Cocktail Approach.Front Pharmacol. 2021 Sep 17;12:726669. doi: 10.3389/fphar.2021.726669. eCollection 2021. Front Pharmacol. 2021. PMID: 34603040 Free PMC article.
-
ABCG2 Is Overexpressed on Red Blood Cells in Ph-Negative Myeloproliferative Neoplasms and Potentiates Ruxolitinib-Induced Apoptosis.Int J Mol Sci. 2021 Mar 29;22(7):3530. doi: 10.3390/ijms22073530. Int J Mol Sci. 2021. PMID: 33805426 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases