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Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects.
Drug Des Devel Ther. 2019; 13:2533-2542.DD

Abstract

Purpose

Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers.

Patients and methods

An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration versus time curve over dosing interval (AUCτ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax,ss and AUCτ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions.

Results

Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Cmax,ss and AUCτ,ss, were 0.9829 (0.8334-1.1590) and 1.0003 (0.9342-1.0710) for telmisartan; 0.9908 (0.9602-1.0223) and 1.0081 (0.9758-1.0413) for amlodipine; and 2.2762 (2.0113-2.5758) and 1.3261 (1.2385-1.4198) for rosuvastatin, respectively.

Conclusion

The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.

Authors+Show Affiliations

Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea.Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.Yuhan Research Institute, Yuhan Corporation, Seoul, Republic of Korea.Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea. Research Institute of Clinical Medicine of Chonbuk National University , Jeonju, Republic of Korea. Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea.

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

31440035

Citation

Moon, Seol Ju, et al. "Pharmacokinetic Interactions Between Telmisartan/amlodipine and Rosuvastatin After Multiple Oral Administrations in Healthy Korean Male Subjects." Drug Design, Development and Therapy, vol. 13, 2019, pp. 2533-2542.
Moon SJ, Jeon JY, Jang K, et al. Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects. Drug Des Devel Ther. 2019;13:2533-2542.
Moon, S. J., Jeon, J. Y., Jang, K., Yu, K. S., Lim, Y., & Kim, M. G. (2019). Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects. Drug Design, Development and Therapy, 13, 2533-2542. https://doi.org/10.2147/DDDT.S210364
Moon SJ, et al. Pharmacokinetic Interactions Between Telmisartan/amlodipine and Rosuvastatin After Multiple Oral Administrations in Healthy Korean Male Subjects. Drug Des Devel Ther. 2019;13:2533-2542. PubMed PMID: 31440035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects. AU - Moon,Seol Ju, AU - Jeon,Ji-Young, AU - Jang,Kyungho, AU - Yu,Kyung-Sang, AU - Lim,Yeji, AU - Kim,Min-Gul, Y1 - 2019/07/25/ PY - 2019/03/28/received PY - 2019/06/12/accepted PY - 2019/8/24/entrez PY - 2019/8/24/pubmed PY - 2020/4/9/medline KW - antihypertensive KW - drug–drug interactions KW - pharmacokinetics KW - phase I KW - statins SP - 2533 EP - 2542 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 13 N2 - Purpose: Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers. Patients and methods: An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration versus time curve over dosing interval (AUCτ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed Cmax,ss and AUCτ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions. Results: Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of Cmax,ss and AUCτ,ss, were 0.9829 (0.8334-1.1590) and 1.0003 (0.9342-1.0710) for telmisartan; 0.9908 (0.9602-1.0223) and 1.0081 (0.9758-1.0413) for amlodipine; and 2.2762 (2.0113-2.5758) and 1.3261 (1.2385-1.4198) for rosuvastatin, respectively. Conclusion: The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/31440035/Pharmacokinetic_interactions_between_telmisartan/amlodipine_and_rosuvastatin_after_multiple_oral_administrations_in_healthy_Korean_male_subjects_ L2 - https://dx.doi.org/10.2147/DDDT.S210364 DB - PRIME DP - Unbound Medicine ER -