Journal Article

Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States

Bujac, Sarah R., Birmingham, Bruce K., Kim, Kenneth, Azumaya, Connie T., Chen, Yusong, Elsby, Robert, Zalikowski, Julie, Ambrose, Helen J.

2015

Overview

Purpose Systemic exposure to rosuvastatin in Asian subjects living in Japan or Singapore is approximately twice that observed in Caucasian subjects in Western countries or in Singapore. This study was conducted to determine whether pharmacokinetic differences exist among the most populous Asian subgroups and Caucasian subjects in the USA. Method Rosuvastatin pharmacokinetics was studied in Chinese, Filipino, Asian-Indian, Korean, Vietnamese, Japanese and Caucasian subjects residing in California. Plasma concentrations of rosuvastatin and metabolites after a single 20-mg dose were determined by mass spectrometric detection. The influence of polymorphisms in SLCO1B1 (T521>C [Val174Ala] and A388>G [Asn130Asp]) and in ABCG2 (C421>A [Gln141Lys]) on exposure to rosuvastatin was also assessed. Results The average rosuvastatin area under the curve from time zero to time of last quantifiable concentration was between 64 and 84 % higher, and maximum drug concentration was between 70 and 98 % higher in East Asian subgroups compared with Caucasians. Data for Asian-Indians was intermediate to these two ethnic groups at 26 and 29 %, respectively. Similar increases in exposure to N-desmethyl rosuvastatin and rosuvastatin lactone were observed. Rosuvastatin exposure was higher in subjects carrying the SLCO1B1 521C allele compared with that in non-carriers of this allele. Similarly, exposure was higher in subjects carrying the ABCG2 421A allele compared with that in non-carriers. Conclusion Plasma exposure to rosuvastatin and its metabolites was significantly higher in Asian populations residing in the USA compared with Caucasian subjects living in the same environment. This study suggests that polymorphisms in the SLCO1B1 and ABCG2 genes contribute to the variability in rosuvastatin exposure.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Alleles / Asian Continental Ancestry Group - genetics / Asian people / ATP Binding Cassette Transporter, Sub-Family G, Member 2 / ATP-Binding Cassette Transporters - genetics / Bioavailability / Biomedical and Life Sciences / Biomedicine / European Continental Ancestry Group - genetics / Female / Genotype / Genotype & phenotype / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects / Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood / Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics / Male / Neoplasm Proteins - genetics / Organic Anion Transporters - genetics / Pharmacokinetics and Disposition / Pharmacology / Pharmacology/Toxicology / Polymorphism, Single Nucleotide - genetics / Rosuvastatin Calcium - adverse effects / Rosuvastatin Calcium - blood / Rosuvastatin Calcium - pharmacokinetics / Solute Carrier Organic Anion Transporter Family Member 1b1 / Statins / United States / White people