Pharmacokinetics of Rosuvastatin/Olmesartan Fixed-Dose Combination: A Single-Dose, Randomized, Open-Label, 2-Period Crossover Study in Healthy Korean Subjects

• Published in: Clinical therapeutics 2013-07, Vol.35 (7), p.915-922
• Main Authors: Son, Hankil, MS, Roh, Hyerang, BS, Lee, Donghwan, MD, Chang, HeeChul, PhD, Kim, JunKu, MS, Yun, Chohee, BS, Park, Kyungsoo, PhD, MD
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Application programming interface; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood pressure; Cardiology. Vascular system; Catheters; Chronic illnesses; combination drug; Cross-Over Studies; Data processing; Drug Combinations; Drug dosages; Drug therapy; Drug Therapy, Combination; dyslipidemia; Fluorobenzenes - administration & dosage; Fluorobenzenes - adverse effects; Fluorobenzenes - pharmacokinetics; Healthy Volunteers; Humans; Hypertension; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - pharmacokinetics; Internal Medicine; Male; Medical Education; Medical sciences; Middle Aged; olmesartan; pharmacokinetics; Pharmacology. Drug treatments; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - pharmacokinetics; rosuvastatin; Rosuvastatin Calcium; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Tetrazoles - administration & dosage; Tetrazoles - adverse effects; Tetrazoles - pharmacokinetics; Young Adult
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2013.05.016

Abstract Background Rosuvastatin, a lipid-lowering agent, has been widely used with olmesartan, a long-acting angiotensin II receptor blocker, indicated for the treatment of dyslipidemia accompanied by hypertension. A fixed-dose combination (FDC) tablet of these 2 drugs was recently developed to enhance the dosing convenience and to increase patient compliance while yielding pharmacokinetic profiles comparable to coadministration of each drug as individual tablets. Objective The goal of present study was to compare the pharmacokinetic profiles of single-dose administration of an FDC tablet containing rosuvastatin/olmesartan 20/40 mg (test formulation) with coadministration of a rosuvastatin 20-mg tablet and a olmesartan 40-mg tablet (reference formulation) in healthy Korean male volunteers, for the purpose of determining bioequivalence. Methods This single-dose, randomized, open-label, 2-period crossover study enrolled subjects aged 20 to 50 years and within 20% of ideal body weight. Each subject received a single dose of the test and reference formulations orally in a fasted state, with a 7-day washout period between the administrations. 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. Bioequivalence was concluded if the 90% CIs of the geometric mean ratios for the primary pharmacokinetic parameters were within the predetermined range of 80% to 125%. Adverse events (AEs) were evaluated based on subject interviews and physical examinations. Results Among the 58 enrolled subjects, 54 completed the study. The 90% CIs of the geometric mean ratios of the primary pharmacokinetic parameters were as follows: rosuvastatin: AUClast , 85.60% to 97.40% and Cmax , 83.16% to 98.21%; N -desmethyl rosuvastatin: AUClast , 82.08% to 93.45% and Cmax , 79.23% to 93.41%; and olmesartan: AUClast , 97.69% to 105.69% and Cmax , 100.35% to 109.42%. The most frequently noted AE was headache, occurring in 3 and 6 patients with the test and reference formulations, respectively. All of the AEs were expected, and there was no significant difference in the prevalences of AEs between the 2 formulations. Conclusions The pharmacokinetic properties of the newly developed FDC tablet of rosuvastatin/olmesartan 20/40 mg suggest that it is bioequivalent to co-administration of each drug as individual tablets in these healthy Korean male subjects. The two