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Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects.
Clin Ther. 2017 Sep; 39(9):1799-1810.CT

Abstract

PURPOSE

Rosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers.

METHODS

This trial was a randomized, open-label, single-dose, 2-way crossover study. The healthy subjects received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each period (periods 1 and 2), with a 14-day washout period. The blood samples for PK analysis were collected predose and up to 96 hours after administration, and safety was assessed throughout the study.

FINDINGS

Sixty-four healthy Korean subjects were enrolled, and 57 subjects completed the study. All subjects were men and mean age was 28.52 ± 5.93. The geometric least squares mean ratios (test/reference) and 90% CIs of Cmax and AUC0-last were 101.54% (94.03-109.65) and 97.71% (91.86-103.93) for rosuvastatin, 108.93% (98.55-120.40) and 102.90% (96.72-109.47) for free ezetimibe, and 106.74% (98.18-116.05) and 104.24 % (99.53-109.17) for total ezetimibe. Twenty-four adverse events (AEs) were reported in 22 subjects. Three cases were related to the study drugs; 2 cases were mild, and 1 case was severe. However, all AEs were resolved without any sequelae. In addition, there were no serious AEs throughout the study.

IMPLICATIONS

The FDC tablet of rosuvastatin/ezetimibe was well tolerated and resulted in comparable systemic exposure with co-administration of rosuvastatin and ezetimibe. ClinicalTrials.gov identifier: NCT02941848.

Authors+Show Affiliations

Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea.Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea; Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.Clinical Research Team, Hanmi Pharmaceutical Co, Ltd, Seoul, South Korea.Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, South Korea; Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, South Korea. Electronic address: delivery98@yuhs.ac.Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: mjchang@yonsei.ac.kr.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28803122

Citation

Min, Kyoung Lok, et al. "Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects." Clinical Therapeutics, vol. 39, no. 9, 2017, pp. 1799-1810.
Min KL, Park MS, Jung J, et al. Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects. Clin Ther. 2017;39(9):1799-1810.
Min, K. L., Park, M. S., Jung, J., Chang, M. J., & Kim, C. O. (2017). Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects. Clinical Therapeutics, 39(9), 1799-1810. https://doi.org/10.1016/j.clinthera.2017.07.038
Min KL, et al. Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects. Clin Ther. 2017;39(9):1799-1810. PubMed PMID: 28803122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects. AU - Min,Kyoung Lok, AU - Park,Min Soo, AU - Jung,Jina, AU - Chang,Min Jung, AU - Kim,Choon Ok, Y1 - 2017/08/10/ PY - 2017/04/06/received PY - 2017/07/13/revised PY - 2017/07/19/accepted PY - 2017/8/15/pubmed PY - 2018/3/3/medline PY - 2017/8/14/entrez KW - ezetimibe KW - fixed-dose combination KW - pharmacokinetics KW - rosuvastatin SP - 1799 EP - 1810 JF - Clinical therapeutics JO - Clin Ther VL - 39 IS - 9 N2 - PURPOSE: Rosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers. METHODS: This trial was a randomized, open-label, single-dose, 2-way crossover study. The healthy subjects received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each period (periods 1 and 2), with a 14-day washout period. The blood samples for PK analysis were collected predose and up to 96 hours after administration, and safety was assessed throughout the study. FINDINGS: Sixty-four healthy Korean subjects were enrolled, and 57 subjects completed the study. All subjects were men and mean age was 28.52 ± 5.93. The geometric least squares mean ratios (test/reference) and 90% CIs of Cmax and AUC0-last were 101.54% (94.03-109.65) and 97.71% (91.86-103.93) for rosuvastatin, 108.93% (98.55-120.40) and 102.90% (96.72-109.47) for free ezetimibe, and 106.74% (98.18-116.05) and 104.24 % (99.53-109.17) for total ezetimibe. Twenty-four adverse events (AEs) were reported in 22 subjects. Three cases were related to the study drugs; 2 cases were mild, and 1 case was severe. However, all AEs were resolved without any sequelae. In addition, there were no serious AEs throughout the study. IMPLICATIONS: The FDC tablet of rosuvastatin/ezetimibe was well tolerated and resulted in comparable systemic exposure with co-administration of rosuvastatin and ezetimibe. ClinicalTrials.gov identifier: NCT02941848. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/28803122/Comparison_of_Pharmacokinetics_and_Safety_of_a_Fixed_dose_Combination_of_Rosuvastatin_and_Ezetimibe_Versus_Separate_Tablets_in_Healthy_Subjects_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(17)30827-5 DB - PRIME DP - Unbound Medicine ER -