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

• Published in: Clinical therapeutics 2014-08, Vol.36 (8), p.1159-1170
• Main Authors: Roh, Hyerang, BS, Son, Hankil, PhD, Lee, Donghwan, MD, PhD, Chang, HeeChul, PhD, Yun, Chohee, BS, Park, Kyungsoo, PhD, MD
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - pharmacokinetics; Area Under Curve; Asian Continental Ancestry Group; Chronic illnesses; Cross-Over Studies; Disease; Drug dosages; Drug Interactions; Drug therapy; Drug Therapy, Combination - adverse effects; drug–drug interaction; Healthy Volunteers; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics; Hypertension; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - pharmacokinetics; Internal Medicine; Male; Medical Education; Middle Aged; olmesartan; pharmacokinetics; Republic of Korea; rosuvastatin; Rosuvastatin Calcium - administration & dosage; Rosuvastatin Calcium - adverse effects; Rosuvastatin Calcium - pharmacokinetics; Tetrazoles - administration & dosage; Tetrazoles - adverse effects; Tetrazoles - pharmacokinetics; Young Adult
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2014.06.022

Abstract 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 coadmini