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Pharmacokinetic comparison of 2 fixed-dose combination tablets of amlodipine and valsartan in healthy male Korean volunteers: a randomized, open-label, 2-period, single-dose, crossover study.
Clin Ther. 2013 Jul; 35(7):934-40.CT

Abstract

BACKGROUND

Amlodipine and valsartan have different mechanisms of action, and it is known that the combination therapy with the 2 drugs increases treatment effects compared with the monotherapy with each drug. A fixed-dose combination (FDC) drug is a formulation including fixed amounts of active drug ingredients combined in a single dosage form that is expected to improve medication compliance.

OBJECTIVE

The goal of this study was to compare the pharmacokinetic profiles of single administration of a newly developed FDC tablet containing amlodipine orotate 10 mg and valsartan 160 mg (test formulation) with the conventional FDC tablet of amlodipine besylate 10 mg and valsartan 160 mg (reference formulation) in healthy male Korean volunteers.

METHODS

This was a randomized, open-label, single-dose, 2-way crossover study. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight. Each subject received a single dose of the reference and the test formulations, with a 14-day washout period between formulations. Blood samples were collected up to 144 hours after the dose, and pharmacokinetic parameters were determined for amlodipine and valsartan. Adverse events were evaluated based on subject interviews and physical examinations.

RESULTS

Forty-eight of the 50 enrolled subjects completed the study. For both amlodipine and valsartan, the primary pharmacokinetic parameters were included in the range for assumed bioequivalence, yielding 90% CI ratios of 0.9277 to 0.9903 for AUC(0-last) and 0.9357 to 1.0068 for C(max) in amlodipine, and 0.9784 to 1.1817 for AUC(0-last) and 0.9738 to 1.2145 for C(max) in valsartan. Dizziness was the most frequently noted adverse event, occurring in 4 subjects with the test formulation, followed by oropharyngeal pain occurring in 1 subject with the test formulation and 3 subjects with the reference formulation. All other adverse events occurred in <3 subjects.

CONCLUSIONS

These findings suggest that the pharmacokinetics of the newly developed FDC tablet of amlodipine and valsartan did not differ significantly from the conventional FDC tablet in these healthy Korean male subjects. Both formulations were well tolerated, with no serious adverse events observed. ClinicalTrials.gov identifier: NCT01823913.

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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23870605

Citation

Kim, Yukyung, et al. "Pharmacokinetic Comparison of 2 Fixed-dose Combination Tablets of Amlodipine and Valsartan in Healthy Male Korean Volunteers: a Randomized, Open-label, 2-period, Single-dose, Crossover Study." Clinical Therapeutics, vol. 35, no. 7, 2013, pp. 934-40.
Kim Y, Son M, Lee D, et al. Pharmacokinetic comparison of 2 fixed-dose combination tablets of amlodipine and valsartan in healthy male Korean volunteers: a randomized, open-label, 2-period, single-dose, crossover study. Clin Ther. 2013;35(7):934-40.
Kim, Y., Son, M., Lee, D., Roh, H., Son, H., Chae, D., Bahng, M. Y., & Park, K. (2013). Pharmacokinetic comparison of 2 fixed-dose combination tablets of amlodipine and valsartan in healthy male Korean volunteers: a randomized, open-label, 2-period, single-dose, crossover study. Clinical Therapeutics, 35(7), 934-40. https://doi.org/10.1016/j.clinthera.2013.05.021
Kim Y, et al. Pharmacokinetic Comparison of 2 Fixed-dose Combination Tablets of Amlodipine and Valsartan in Healthy Male Korean Volunteers: a Randomized, Open-label, 2-period, Single-dose, Crossover Study. Clin Ther. 2013;35(7):934-40. PubMed PMID: 23870605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic comparison of 2 fixed-dose combination tablets of amlodipine and valsartan in healthy male Korean volunteers: a randomized, open-label, 2-period, single-dose, crossover study. AU - Kim,Yukyung, AU - Son,Mijeong, AU - Lee,Donghwan, AU - Roh,Hyerang, AU - Son,Hankil, AU - Chae,Dongwoo, AU - Bahng,Mi Young, AU - Park,Kyungsoo, PY - 2013/05/09/received PY - 2013/05/18/revised PY - 2013/05/30/accepted PY - 2013/7/23/entrez PY - 2013/7/23/pubmed PY - 2014/1/28/medline KW - amlodipine KW - combination drug KW - pharmacokinetic KW - valsartan SP - 934 EP - 40 JF - Clinical therapeutics JO - Clin Ther VL - 35 IS - 7 N2 - BACKGROUND: Amlodipine and valsartan have different mechanisms of action, and it is known that the combination therapy with the 2 drugs increases treatment effects compared with the monotherapy with each drug. A fixed-dose combination (FDC) drug is a formulation including fixed amounts of active drug ingredients combined in a single dosage form that is expected to improve medication compliance. OBJECTIVE: The goal of this study was to compare the pharmacokinetic profiles of single administration of a newly developed FDC tablet containing amlodipine orotate 10 mg and valsartan 160 mg (test formulation) with the conventional FDC tablet of amlodipine besylate 10 mg and valsartan 160 mg (reference formulation) in healthy male Korean volunteers. METHODS: This was a randomized, open-label, single-dose, 2-way crossover study. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight. Each subject received a single dose of the reference and the test formulations, with a 14-day washout period between formulations. Blood samples were collected up to 144 hours after the dose, and pharmacokinetic parameters were determined for amlodipine and valsartan. Adverse events were evaluated based on subject interviews and physical examinations. RESULTS: Forty-eight of the 50 enrolled subjects completed the study. For both amlodipine and valsartan, the primary pharmacokinetic parameters were included in the range for assumed bioequivalence, yielding 90% CI ratios of 0.9277 to 0.9903 for AUC(0-last) and 0.9357 to 1.0068 for C(max) in amlodipine, and 0.9784 to 1.1817 for AUC(0-last) and 0.9738 to 1.2145 for C(max) in valsartan. Dizziness was the most frequently noted adverse event, occurring in 4 subjects with the test formulation, followed by oropharyngeal pain occurring in 1 subject with the test formulation and 3 subjects with the reference formulation. All other adverse events occurred in <3 subjects. CONCLUSIONS: These findings suggest that the pharmacokinetics of the newly developed FDC tablet of amlodipine and valsartan did not differ significantly from the conventional FDC tablet in these healthy Korean male subjects. Both formulations were well tolerated, with no serious adverse events observed. ClinicalTrials.gov identifier: NCT01823913. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/23870605/Pharmacokinetic_comparison_of_2_fixed_dose_combination_tablets_of_amlodipine_and_valsartan_in_healthy_male_Korean_volunteers:_a_randomized_open_label_2_period_single_dose_crossover_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(13)00309-3 DB - PRIME DP - Unbound Medicine ER -