Rosuvastatin Pharmacokinetics in Asian and White Subjects Wild Type for Both OATP1B1 and BCRP Under Control and Inhibited Conditions

• Published in: Journal of pharmaceutical sciences Vol. 106; no. 9; pp. 2751 - 2757
• Main Authors: Wu, Hsin-Fang, Hristeva, Nadya, Chang, Jae, Liang, Xiaorong, Li, Ruina, Frassetto, Lynda, Benet, Leslie Z.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: ABC transporters; Adult; Aged; Anticholesteremic Agents - blood; Asian People - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics; clinical pharmacokinetics; Cross-Over Studies; drug interaction; efflux pumps; Female; Genotype; hepatic transport; Humans; intestinal absorption; Liver-Specific Organic Anion Transporter 1 - genetics; Male; Middle Aged; Neoplasm Proteins - genetics; organic anion-transporting polypeptide transporters; Polymorphism, Single Nucleotide; race; Rosuvastatin Calcium - blood; White People - genetics; Young Adult; race; drug interaction; clinical pharmacokinetics; ABC transporters; organic anion-transporting polypeptide transporters; intestinal absorption; efflux pumps; hepatic transport
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2017.03.027

The Food and Drug Administration recommends rosuvastatin dosage reductions in Asian patients because pharmacokinetic studies have demonstrated an approximate 2-fold increase in median exposure to rosuvastatin in Asian subjects compared with Caucasian controls. Yet, no explanation for this ethnic difference has been confirmed. Here we show that rosuvastatin exposure in Asians and Whites does not differ significantly when all subjects are wild-type carriers for both solute carrier organic anion transporter 1B1 *1a and ATP-binding cassette subfamily G member 2 c.421 transporters in a 2-arm, randomized, cross-over rosuvastatin pharmacokinetics study in healthy white and Asian volunteers. For single rosuvastatin doses, AUC0-48 were 92.5 (±36.2) and 83.5 (±32.2) ng/mL × h and Cmax were 10.0 (±4.1) and 7.6 (±3.0) ng/mL for Asians and Whites, respectively. When transporters were inhibited by intravenous rifampin, rosuvastatin AUC0-48 and Cmax also showed no ethnic differences. Our study suggests that both SLCO1B1 and ABCG2 polymorphisms are better predictors of rosuvastatin exposure than ethnicity alone and could be considered in precision medicine dosing of rosuvastatin.