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Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.
Clin Ther. 2013 Jul; 35(7):915-22.CT

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: AUC(last), 85.60% to 97.40% and C(max), 83.16% to 98.21%; N-desmethyl rosuvastatin: AUC(last), 82.08% to 93.45% and C(max), 79.23% to 93.41%; and olmesartan: AUC(last), 97.69% to 105.69% and C(max), 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 formulations were well tolerated, with no serious AEs observed. ClinicalTrials.gov identifier: NCT01823900.

Authors+Show Affiliations

Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23810276

Citation

Son, Hankil, et al. "Pharmacokinetics of Rosuvastatin/olmesartan Fixed-dose Combination: a Single-dose, Randomized, Open-label, 2-period Crossover Study in Healthy Korean Subjects." Clinical Therapeutics, vol. 35, no. 7, 2013, pp. 915-22.
Son H, Roh H, Lee D, et al. Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects. Clin Ther. 2013;35(7):915-22.
Son, H., Roh, H., Lee, D., Chang, H., Kim, J., Yun, C., & Park, K. (2013). Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects. Clinical Therapeutics, 35(7), 915-22. https://doi.org/10.1016/j.clinthera.2013.05.016
Son H, et al. Pharmacokinetics of Rosuvastatin/olmesartan Fixed-dose Combination: a Single-dose, Randomized, Open-label, 2-period Crossover Study in Healthy Korean Subjects. Clin Ther. 2013;35(7):915-22. PubMed PMID: 23810276.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of rosuvastatin/olmesartan fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects. AU - Son,Hankil, AU - Roh,Hyerang, AU - Lee,Donghwan, AU - Chang,Heechul, AU - Kim,Junku, AU - Yun,Chohee, AU - Park,Kyungsoo, Y1 - 2013/06/27/ PY - 2013/05/03/received PY - 2013/05/15/revised PY - 2013/05/21/accepted PY - 2013/7/2/entrez PY - 2013/7/3/pubmed PY - 2014/1/28/medline KW - combination drug KW - dyslipidemia KW - hypertension KW - olmesartan KW - pharmacokinetics KW - rosuvastatin SP - 915 EP - 22 JF - Clinical therapeutics JO - Clin Ther VL - 35 IS - 7 N2 - 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: AUC(last), 85.60% to 97.40% and C(max), 83.16% to 98.21%; N-desmethyl rosuvastatin: AUC(last), 82.08% to 93.45% and C(max), 79.23% to 93.41%; and olmesartan: AUC(last), 97.69% to 105.69% and C(max), 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 formulations were well tolerated, with no serious AEs observed. ClinicalTrials.gov identifier: NCT01823900. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/23810276/Pharmacokinetics_of_rosuvastatin/olmesartan_fixed_dose_combination:_a_single_dose_randomized_open_label_2_period_crossover_study_in_healthy_Korean_subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(13)00268-3 DB - PRIME DP - Unbound Medicine ER -