title: Pharmacokinetic interactions between glimepiride and rosuvastatin in healthy Korean subjects: does theSLCO1B1orCYP2C9genetic polymorphism affect these drug interactions?
abstract: To improve cardiovascular outcomes, dyslipidemia in patients with diabetes needs to be treated. Thus, these patients are likely to take glimepiride and rosuvastatin concomitantly. Therefore, this study aimed to evaluate the pharmacokinetic (PK) interactions between these two drugs in healthy males and to explore the effect ofSLCO1B1andCYP2C9polymorphisms on their interactions in two randomized, open-label crossover studies. Glimepiride was studied in part 1 and rosuvastatin in part 2. Twenty-four participants were randomly assigned to each part. All subjects (n=24) completed part 1, and 22 subjects completed part 2. A total of 38 subjects among the participants of the PK interaction studies were enrolled in the genotype study to analyze theirSLCO1B1andCYP2C9polymorphisms retrospectively (n=22 in part 1, n=16 in part 2). Comparison of the PK and safety of each drug alone with those of the drugs in combination showed that both glimepiride and rosuvastatin did not interact with each other and had tolerable safety profiles in all subjects. However, with regard to glimepiride PK, theSLCO1B1 521TCgroup had a significantly higher maximum plasma concentration (Cmax,ss) and area under the plasma concentration-time curve during the dose interval at steady state (AUCτ,ss) for glimepiride in combination with rosuvastatin than those for glimepiride alone. However, other significant effects of theSLCO1B1orCYP2C9polymorphism on the interaction between the two drugs were not observed. In conclusion, there were no significant PK interactions between the two drugs; however, the exposure to glimepiride could be affected by rosuvastatin in the presence of theSLCO1B1polymorphism.
authors.affiliation: Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul.
authors.forename: Choon Ok
authors.initials: CO
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Medicine and Regulatory Sciences, College of Medicine and Pharmacy, Yonsei University, Incheon.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Oh
authors.affiliation: Korea Medicine Research Institute, Inc., Seongnam.
authors.forename: Hohyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul; Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Park
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9 / Q000097:blood / Q000235:genetics*; D004347:Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D011110:Polymorphism, Genetic / Q000235:genetics*; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D027381:Liver-Specific Organic Anion Transporter 1; C503999:SLCO1B1 protein, human; D013453:Sulfonylurea Compounds; C057619:glimepiride; D000068718:Rosuvastatin Calcium; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9
keywords: CYP2C9; SLCO1B1; glimepiride; pharmacokinetics; rosuvastatin