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Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects.
Drug Des Devel Ther. 2018; 12:1157-1164.DD

Abstract

Objective

The aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects.

Results

This was an open-label, randomized, three-sequence, three-period replicated crossover study in healthy male subjects. The replicated crossover design was done because of high coefficient of variation of PK parameter for fimasartan, that is, >30%. With a 14 days washout period, an FDC tablet containing 60 mg fimasartan, 10 mg amlodipine, and 20 mg rosuvastatin was administered only once, and separate formulations of fimasartan/amlodipine 60 mg/10 mg FDC tablet and 20 mg rosuvastatin tablet administered twice. Blood samples were collected up to 72 hours following drug administration. The plasma concentrations of fimasartan, amlodipine, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was assessed by evaluating vital signs, clinical laboratory parameters, physical examinations, and medical interviews.

Results

The geometric mean ratios and 90% confidence intervals (CIs) for the maximum plasma concentration (Cmax) and area under the curve from time zero to the last measurable sampling time (AUCt) were 1.0776 (0.9201-1.2622) and 0.9978 (0.9538-1.0439) for fimasartan, 1.0038 (0.9782-1.0301) and 1.0055 (0.9828-1.0288) for amlodipine, and 1.0006 (0.9290-1.0776) and 0.9986 (0.9532-1.0461) for rosuvastatin, respectively. A total of 22 adverse events (AEs) were reported by 60 subjects; there were no significant differences in the incidence of AEs between the two groups.

Conclusion

The 90% CI of the Cmax of fimasartan was within the widened acceptance limit, ln(0.6984)-ln(1.4319). The 90% CIs of the other PK parameters for drugs were between ln(0.8) and ln(1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile, to the co-administration of its three constituent drugs.

Authors+Show Affiliations

Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea. Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea.Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea.Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea. Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea.Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea. Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea.

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

29780236

Citation

Oh, Minkyung, et al. "Pharmacokinetic Comparison of a Fixed-dose Combination Versus Concomitant Administration of Fimasartan, Amlodipine, and Rosuvastatin Using Partial Replicated Design in Healthy Adult Subjects." Drug Design, Development and Therapy, vol. 12, 2018, pp. 1157-1164.
Oh M, Ghim JL, Park SE, et al. Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects. Drug Des Devel Ther. 2018;12:1157-1164.
Oh, M., Ghim, J. L., Park, S. E., Kim, E. Y., & Shin, J. G. (2018). Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects. Drug Design, Development and Therapy, 12, 1157-1164. https://doi.org/10.2147/DDDT.S164215
Oh M, et al. Pharmacokinetic Comparison of a Fixed-dose Combination Versus Concomitant Administration of Fimasartan, Amlodipine, and Rosuvastatin Using Partial Replicated Design in Healthy Adult Subjects. Drug Des Devel Ther. 2018;12:1157-1164. PubMed PMID: 29780236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects. AU - Oh,Minkyung, AU - Ghim,Jong-Lyul, AU - Park,Sung-Eun, AU - Kim,Eun-Young, AU - Shin,Jae-Gook, Y1 - 2018/05/08/ PY - 2018/5/22/entrez PY - 2018/5/22/pubmed PY - 2018/10/12/medline KW - bioequivalence KW - fimasartan KW - fixed-dose combination KW - pharmacokinetics KW - replicated crossover SP - 1157 EP - 1164 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 12 N2 - Objective: The aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects. Results: This was an open-label, randomized, three-sequence, three-period replicated crossover study in healthy male subjects. The replicated crossover design was done because of high coefficient of variation of PK parameter for fimasartan, that is, >30%. With a 14 days washout period, an FDC tablet containing 60 mg fimasartan, 10 mg amlodipine, and 20 mg rosuvastatin was administered only once, and separate formulations of fimasartan/amlodipine 60 mg/10 mg FDC tablet and 20 mg rosuvastatin tablet administered twice. Blood samples were collected up to 72 hours following drug administration. The plasma concentrations of fimasartan, amlodipine, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was assessed by evaluating vital signs, clinical laboratory parameters, physical examinations, and medical interviews. Results: The geometric mean ratios and 90% confidence intervals (CIs) for the maximum plasma concentration (Cmax) and area under the curve from time zero to the last measurable sampling time (AUCt) were 1.0776 (0.9201-1.2622) and 0.9978 (0.9538-1.0439) for fimasartan, 1.0038 (0.9782-1.0301) and 1.0055 (0.9828-1.0288) for amlodipine, and 1.0006 (0.9290-1.0776) and 0.9986 (0.9532-1.0461) for rosuvastatin, respectively. A total of 22 adverse events (AEs) were reported by 60 subjects; there were no significant differences in the incidence of AEs between the two groups. Conclusion: The 90% CI of the Cmax of fimasartan was within the widened acceptance limit, ln(0.6984)-ln(1.4319). The 90% CIs of the other PK parameters for drugs were between ln(0.8) and ln(1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile, to the co-administration of its three constituent drugs. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/29780236/Pharmacokinetic_comparison_of_a_fixed_dose_combination_versus_concomitant_administration_of_fimasartan_amlodipine_and_rosuvastatin_using_partial_replicated_design_in_healthy_adult_subjects_ L2 - https://dx.doi.org/10.2147/DDDT.S164215 DB - PRIME DP - Unbound Medicine ER -