PMID- 29780236
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20240314
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 12
DP  - 2018
TI  - Pharmacokinetic comparison of a fixed-dose combination versus concomitant 
      administration of fimasartan, amlodipine, and rosuvastatin using partial 
      replicated design in healthy adult subjects.
PG  - 1157-1164
LID - 10.2147/DDDT.S164215 [doi]
AB  - 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 (C(max)) and area under the curve from time zero to the last 
      measurable sampling time (AUC(t)) 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 C(max) 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.
FAU - Oh, Minkyung
AU  - Oh M
AD  - Department of Pharmacology and PharmacoGenomics Research Center, Inje University 
      College of Medicine, Busan, Republic of Korea.
FAU - Ghim, Jong-Lyul
AU  - Ghim JL
AD  - Department of Pharmacology and PharmacoGenomics Research Center, Inje University 
      College of Medicine, Busan, Republic of Korea.
AD  - Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, 
      Republic of Korea.
FAU - Park, Sung-Eun
AU  - Park SE
AD  - Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, 
      Republic of Korea.
FAU - Kim, Eun-Young
AU  - Kim EY
AD  - Department of Pharmacology and PharmacoGenomics Research Center, Inje University 
      College of Medicine, Busan, Republic of Korea.
AD  - Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, 
      Republic of Korea.
FAU - Shin, Jae-Gook
AU  - Shin JG
AD  - Department of Pharmacology and PharmacoGenomics Research Center, Inje University 
      College of Medicine, Busan, Republic of Korea.
AD  - Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, 
      Republic of Korea.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20180508
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Drug Combinations)
RN  - 0 (Pyrimidines)
RN  - 0 (Tetrazoles)
RN  - 1J444QC288 (Amlodipine)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
RN  - P58222188P (fimasartan)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Amlodipine/administration & dosage/*pharmacokinetics
MH  - Biphenyl Compounds/administration & dosage/*pharmacokinetics
MH  - Drug Combinations
MH  - *Drug Design
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyrimidines/administration & dosage/*pharmacokinetics
MH  - Republic of Korea
MH  - Rosuvastatin Calcium/administration & dosage/*pharmacokinetics
MH  - Tetrazoles/administration & dosage/*pharmacokinetics
MH  - Young Adult
PMC - PMC5951219
OTO - NOTNLM
OT  - bioequivalence
OT  - fimasartan
OT  - fixed-dose combination
OT  - pharmacokinetics
OT  - replicated crossover
COIS- Disclosure All authors report no conflicts of interest in this work.
EDAT- 2018/05/22 06:00
MHDA- 2018/10/12 06:00
PMCR- 2018/05/08
CRDT- 2018/05/22 06:00
PHST- 2018/05/22 06:00 [entrez]
PHST- 2018/05/22 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2018/05/08 00:00 [pmc-release]
AID - dddt-12-1157 [pii]
AID - 10.2147/DDDT.S164215 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2018 May 8;12:1157-1164. doi: 10.2147/DDDT.S164215. 
      eCollection 2018.