title: Rosuvastatin Pharmacokinetics in Asian and White Subjects Wild Type for Both OATP1B1 and BCRP Under Control and Inhibited Conditions.
abstract: 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, AUC0-48were 92.5 (±36.2) and 83.5 (±32.2) ng/mL × h and Cmaxwere 10.0 (±4.1) and 7.6 (±3.0) ng/mL for Asians and Whites, respectively. When transporters were inhibited by intravenous rifampin, rosuvastatin AUC0-48and Cmaxalso 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.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94143.
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Wu
authors.affiliation: School of Pharmacy, University of California, San Francisco, San Francisco, California 94143.
authors.forename: Nadya
authors.initials: N
authors.lastname: Hristeva
authors.affiliation: Drug Metabolism and Pharmacokinetics, Genentech Inc. South San Francisco, California 94080.
authors.forename: Jae
authors.initials: J
authors.lastname: Chang
authors.affiliation: Drug Metabolism and Pharmacokinetics, Genentech Inc. South San Francisco, California 94080.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Drug Metabolism and Pharmacokinetics, Genentech Inc. South San Francisco, California 94080.
authors.forename: Ruina
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California 94143.
authors.forename: Lynda
authors.initials: L
authors.lastname: Frassetto
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94143. Electronic address: leslie.benet@ucsf.edu.
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000097:blood*; D044466:Asian People / Q000235:genetics; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000068718:Rosuvastatin Calcium / Q000097:blood*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000924:Anticholesteremic Agents; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; C503999:SLCO1B1 protein, human; D000068718:Rosuvastatin Calcium
keywords: ABC transporters; clinical pharmacokinetics; drug interaction; efflux pumps; hepatic transport; intestinal absorption; organic anion-transporting polypeptide transporters; race