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Pharmacokinetic Interactions Between the Fixed-Dose Combination of Ezetimibe/Rosuvastatin 10/20 Mg and the Fixed-Dose Combination of Telmisartan/Amlodipine 80/5 Mg in Healthy Subjects.

التفاصيل البيبلوغرافية
العنوان: Pharmacokinetic Interactions Between the Fixed-Dose Combination of Ezetimibe/Rosuvastatin 10/20 Mg and the Fixed-Dose Combination of Telmisartan/Amlodipine 80/5 Mg in Healthy Subjects.
المؤلفون: Ryu H; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea., Kim HC; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea., Jeon I; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea., Jang IJ; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea., Cho JY; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea., Kim KT; Addpharma, Inc., Yongin-si, Gyeonggi-do, Republic of Korea., Oh J; Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.; Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of Korea.; Clinical Research Institute, Jeju National University Hospital, Jeju, Republic of Korea.
المصدر: Drug design, development and therapy [Drug Des Devel Ther] 2024 Jul 01; Vol. 18, pp. 2641-2652. Date of Electronic Publication: 2024 Jul 01 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Dove Press Limited Country of Publication: New Zealand NLM ID: 101475745 Publication Model: eCollection Cited Medium: Internet ISSN: 1177-8881 (Electronic) Linking ISSN: 11778881 NLM ISO Abbreviation: Drug Des Devel Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Auckland, N.Z.] : Dove Press Limited
مواضيع طبية MeSH: Telmisartan*/administration & dosage , Telmisartan*/pharmacokinetics , Rosuvastatin Calcium*/pharmacokinetics , Rosuvastatin Calcium*/administration & dosage , Amlodipine*/pharmacokinetics , Amlodipine*/administration & dosage , Ezetimibe*/administration & dosage , Ezetimibe*/pharmacokinetics , Cross-Over Studies* , Healthy Volunteers* , Drug Combinations*, Humans ; Male ; Adult ; Young Adult ; Benzoates/pharmacokinetics ; Benzoates/administration & dosage ; Benzimidazoles/pharmacokinetics ; Benzimidazoles/administration & dosage ; Dose-Response Relationship, Drug ; Drug Interactions
مستخلص: Background: Management of hypertension and hyperlipidemia, which are common comorbid risk factors for cardiovascular diseases, require multiple medications. The development of a fixed-dose combination (FDC) containing ezetimibe, rosuvastatin, telmisartan, and amlodipine aims to enhance patient adherence and persistence, but the potential interactions among the four medications have not been studied. This study aimed to evaluate the pharmacokinetic (PK) interactions between the FDC of ezetimibe/rosuvastatin 10/20 mg (ER) and the FDC of telmisartan/amlodipine 80/5 mg (TA).
Methods: An open-label, single-sequence, three-period, three-treatment crossover study was conducted in healthy male subjects. All subjects received ER for 7 days, TA for 9 days and ER combined with TA for 7 days during each treatment period. For PK analysis of total/free ezetimibe, rosuvastatin, telmisartan, and amlodipine, serial blood samples were collected for 24 hours at steady state. Safety profiles were assessed throughout the study.
Results: Thirty-eight subjects were enrolled, and 34 subjects completed the study. The systemic exposure to each active ingredient after coadministration of the two FDCs was similar to that after each FDC alone. The geometric mean ratios and 90% confidence intervals for the maximum plasma concentration (µg/L) and the area under the plasma concentration-time curve (h·µg/L) of the combination therapy to monotherapy, assessed at steady state, were as follows: total ezetimibe, 1.0264 (0.8765-1.2017) and 0.9359 (0.7847-1.1163); free ezetimibe, 1.5713 (1.2821-1.9257) and 0.9941 (0.8384-1.1788); rosuvastatin, 2.1673 (1.7807-2.6379) and 1.1714 (0.9992-1.3733); telmisartan, 1.0745 (0.8139-1.4186) and 1.1057 (0.8379-1.4591); and amlodipine, 0.9421 (0.8764-1.0126) and 0.9603 (0.8862-1.0405). Both combination therapy and monotherapy were well tolerated by the subjects.
Conclusion: The coadministration of ezetimibe/rosuvastatin 10/20 mg and ezetimibe/rosuvastatin 10/20 mg was well tolerated in healthy subjects, and the PK interaction between those two FDCs was not clinically significant.
Competing Interests: Kyung Tae Kim is a full-time employee of Addpharma. The other authors report no conflicts of interest associated with this work.
(© 2024 Ryu et al.)
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فهرسة مساهمة: Keywords: amlodipine; drug‒drug interactions; ezetimibe; fixed-dose combination; pharmacokinetics; rosuvastatin; telmisartan
المشرفين على المادة: U5SYW473RQ (Telmisartan)
83MVU38M7Q (Rosuvastatin Calcium)
1J444QC288 (Amlodipine)
EOR26LQQ24 (Ezetimibe)
0 (Drug Combinations)
0 (Benzoates)
0 (Benzimidazoles)
تواريخ الأحداث: Date Created: 20240708 Date Completed: 20240708 Latest Revision: 20240709
رمز التحديث: 20240709
مُعرف محوري في PubMed: PMC11225994
DOI: 10.2147/DDDT.S465652
PMID: 38974125
قاعدة البيانات: MEDLINE
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