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Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.
Drug Des Devel Ther. 2018; 12:545-553.DD

Abstract

Purpose

A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance.

Methods

The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.

Results

Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0-t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study.

Conclusion

CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments.

Authors+Show Affiliations

Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea. Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea.Analytical Research Division, Biocore Co Ltd, Seoul, Republic of Korea.Department of Molecular Medicine, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea. Department of Biomedical Science, BK21 Plus KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduate School, Daegu, Republic of Korea.Division of Cardiology, Department of Internal Medicine, Kyungpook National University School of Medicine & Hospital, Daegu, Republic of Korea.Clinical Trial Center, Kyungpook National University Hospital, Daegu, Republic of Korea.

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

29559771

Citation

Kang, Woo Youl, et al. "Pharmacokinetic and Bioequivalence Study of a telmisartan/S-amlodipine Fixed-dose Combination (CKD-828) Formulation and Coadministered Telmisartan and S-amlodipine in Healthy Subjects." Drug Design, Development and Therapy, vol. 12, 2018, pp. 545-553.
Kang WY, Seong SJ, Ohk B, et al. Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects. Drug Des Devel Ther. 2018;12:545-553.
Kang, W. Y., Seong, S. J., Ohk, B., Gwon, M. R., Kim, B. K., La, S., Kim, H. J., Cho, S., Yoon, Y. R., Yang, D. H., & Lee, H. W. (2018). Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects. Drug Design, Development and Therapy, 12, 545-553. https://doi.org/10.2147/DDDT.S156492
Kang WY, et al. Pharmacokinetic and Bioequivalence Study of a telmisartan/S-amlodipine Fixed-dose Combination (CKD-828) Formulation and Coadministered Telmisartan and S-amlodipine in Healthy Subjects. Drug Des Devel Ther. 2018;12:545-553. PubMed PMID: 29559771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic and bioequivalence study of a telmisartan/S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects. AU - Kang,Woo Youl, AU - Seong,Sook Jin, AU - Ohk,Boram, AU - Gwon,Mi-Ri, AU - Kim,Bo Kyung, AU - La,Sookie, AU - Kim,Hyun-Ju, AU - Cho,Seungil, AU - Yoon,Young-Ran, AU - Yang,Dong Heon, AU - Lee,Hae Won, Y1 - 2018/03/14/ PY - 2018/3/22/entrez PY - 2018/3/22/pubmed PY - 2018/9/18/medline KW - S-amlodipine KW - fixed-dose combination KW - pharmacokinetics KW - safety KW - telmisartan SP - 545 EP - 553 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 12 N2 - Purpose: A new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance. Methods: The pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period. Results: Forty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0-t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study. Conclusion: CKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/29559771/Pharmacokinetic_and_bioequivalence_study_of_a_telmisartan/S_amlodipine_fixed_dose_combination__CKD_828__formulation_and_coadministered_telmisartan_and_S_amlodipine_in_healthy_subjects_ L2 - https://dx.doi.org/10.2147/DDDT.S156492 DB - PRIME DP - Unbound Medicine ER -