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Pharmacokinetic Interaction Between Rosuvastatin and Olmesartan: A Randomized, Open-label, 3-period, Multiple-dose Crossover Study in Healthy Korean Male Subjects

 Hyerang Roh  ;  Hankil Son  ;  Donghwan Lee  ;  HeeChul Chang  ;  Chohee Yun  ;  Kyungsoo Park 
 CLINICAL THERAPEUTICS, Vol.36(8) : 1159-1170, 2014 
Journal Title
Issue Date
Administration, Oral ; Adult ; Antihypertensive Agents/administration & dosage ; Antihypertensive Agents/adverse effects ; Antihypertensive Agents/pharmacokinetics* ; Area Under Curve ; Asian Continental Ancestry Group ; Cross-Over Studies ; Drug Interactions ; Drug Therapy, Combination/adverse effects ; Healthy Volunteers ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics* ; Imidazoles/administration & dosage ; Imidazoles/adverse effects ; Imidazoles/pharmacokinetics* ; Male ; Middle Aged ; Republic of Korea ; Rosuvastatin Calcium/administration & dosage ; Rosuvastatin Calcium/adverse effects ; Rosuvastatin Calcium/pharmacokinetics* ; Tetrazoles/administration & dosage ; Tetrazoles/adverse effects ; Tetrazoles/pharmacokinetics* ; Young Adult
drug–drug interaction ; olmesartan ; pharmacokinetics ; rosuvastatin
PURPOSE: Rosuvastatin has been widely used in combination with olmesartan for the treatment of dyslipidemia accompanied by hypertension. With no information currently available on the interaction between the 2 drugs, a pharmacokinetic study was conducted to investigate the influence of rosuvastatin on olmesartan and vice versa when the 2 drugs were coadministered. The purpose of this study was to investigate the pharmacokinetic profile of coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet and the associated drug-drug interaction in healthy Korean male volunteers. METHODS: This was a randomized, open-label, 3-period, multiple-dose crossover study. Eligible subjects were aged 20 to 50 years and within 20% of their ideal body weight. After being randomly assigned to 6 groups of equal number, subjects received each of the following 3 formulations once a day for 7 consecutive days with an 8-day washout period between the formulations: rosuvastatin 20-mg tablet, olmesartan 40-mg tablet, and coadministration of the rosuvastatin 20-mg tablet and the olmesartan 40-mg tablet. Blood samples were collected up to 72 hours after dosing, and pharmacokinetic parameters were determined for rosuvastatin, its active metabolite (N-desmethyl rosuvastatin), and olmesartan. Adverse events were evaluated based on subject interviews and physical examinations. FINDINGS: Among the 36 enrolled subjects, 34 completed the study (mean [range] age, 28.6 [23-49] y; mean [range] weight, 66.4 [52.2-78.7] kg). The 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters for the coadministration of the 2 drugs to the mono-administration of each drug were 85.14% to 96.08% for AUCτ and 81.41% to 97.48% for Css,max for rosuvastatin, and 77.55% to 89.48% for AUCτ and 75.62% to 90.12% for Css,max for N-desmethyl rosuvastatin; those values were 95.61% to 102.57% for AUCτ and 91.73% to 102.98% for Css,max for olmesartan. Dizziness was the most frequently noted adverse drug reaction, occurring in 1 subject receiving mono-administration of rosuvastatin, 1 subject receiving mono-administration of olmesartan, and 4 subjects receiving coadministration of rosuvastatin and olmesartan. All the adverse events were expected, and there was no significant difference in the incidence between the 2 formulations. IMPLICATIONS: This study suggests that rosuvastatin and olmesartan did not significantly influence each other's pharmacokinetics when coadministered. Although the pharmacokinetics of N-desmethyl rosuvastatin were influenced by olmesartan, such interactions were considered clinically insignificant. All 3 formulations were well tolerated, and no serious adverse events or drug reactions were noted.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Roh, Hye Rang(노혜랑)
Park, Kyungsoo(박경수) ORCID logo https://orcid.org/0000-0002-6972-1143
Son, Han kil(손한길)
Lee, Dong Hwan(이동환)
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