PMID- 29670335
OWN - NLM
STAT- MEDLINE
DCOM- 20180917
LR  - 20221207
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 12
DP  - 2018
TI  - Evaluation of drug interactions between fimasartan and rosuvastatin after single 
      and multiple doses in healthy Caucasians.
PG  - 787-794
LID - 10.2147/DDDT.S145339 [doi]
AB  - OBJECTIVES: As hypercholesterolemia is often accompanied by hypertension, statins 
      are usually prescribed with angiotensin receptor blockers in clinical practice. 
      This study was performed to evaluate the pharmacokinetics and safety of 
      fimasartan and rosuvastatin when coadministered or administered alone as a single 
      dose or as multiple doses to healthy Caucasians. METHODS: Thirty-six subjects 
      were enrolled into an open-labeled, randomized, 6-sequence, 3-period, 3-way 
      crossover study, and randomly received fimasartan (120 mg), rosuvastatin (20 mg) 
      or both. Blood samples for pharmacokinetics were collected up to 48 hours for 
      fimasartan and 72 hours for rosuvastatin after the last dosing and plasma 
      concentrations of study drugs were determined by liquid chromatography-tandem 
      mass spectrometry. Maximum plasma concentration (C(max)), area under the 
      concentration-time curve (AUC) from 0 to the last measurable time (AUC(last)), 
      maximum plasma concentration at steady state (C(max,ss)) and AUC to the end of 
      the dosing period at steady state (AUC(tau,ss)) were estimated using a 
      non-compartmental method. Safety and tolerability were evaluated throughout the 
      study. RESULTS: Thirty subjects completed the study. After single dose 
      administration, the geometric mean ratio (GMR) and 90% confidence intervals (CIs) 
      of fimasartan with or without rosuvastatin were 0.95 (0.80-1.14) and 0.98 
      (0.91-1.07) for C(max) and AUC(last), respectively. The corresponding values for 
      rosuvastatin with or without fimasartan were 1.32 (1.16-1.50) and 0.97 
      (0.89-1.05), respectively. After administration of multiple doses, the GMRs (90% 
      CIs) for C(max,ss) and AUC(tau,ss) of fimasartan with or without rosuvastatin were 
      0.94 (0.74-1.20) and 1.07 (0.90-1.16), respectively. The corresponding values for 
      rosuvastatin with or without fimasartan were 1.16 (1.02-1.32) and 0.86 
      (0.79-0.94), respectively. A total of 74 adverse events (AEs) were reported and 
      incidences of AEs did not increase significantly with co-administration. 
      CONCLUSION: Co-administration of fimasartan and rosuvastatin did not result in 
      clinically relevant changes in the systemic exposure of fimasartan or 
      rosuvastatin after single and multiple administrations, and they were well 
      tolerated.
FAU - Lee, Jieon
AU  - Lee J
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      Hospital, Seoul National University College of Medicine, Seoul, Republic of 
      Korea.
FAU - Rhee, Su-Jin
AU  - Rhee SJ
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      Hospital, Seoul National University College of Medicine, Seoul, Republic of 
      Korea.
FAU - Lee, SeungHwan
AU  - Lee S
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      Hospital, Seoul National University College of Medicine, Seoul, Republic of 
      Korea.
FAU - Yu, Kyung-Sang
AU  - Yu KS
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      Hospital, Seoul National University College of Medicine, Seoul, Republic of 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20180406
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Pyrimidines)
RN  - 0 (Tetrazoles)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
RN  - P58222188P (fimasartan)
SB  - IM
MH  - Adult
MH  - Biphenyl Compounds/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyrimidines/*administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Rosuvastatin Calcium/*administration & dosage/adverse 
      effects/blood/*pharmacokinetics
MH  - Tetrazoles/*administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - White People
MH  - Young Adult
PMC - PMC5896677
OTO - NOTNLM
OT  - angiotensin II receptor antagonist
OT  - clinical trial
OT  - drug interaction
OT  - fimasartan
OT  - healthy subjects
OT  - rosuvastatin
COIS- Disclosure The authors report no conflicts of interest in this work.
EDAT- 2018/04/20 06:00
MHDA- 2018/09/18 06:00
PMCR- 2018/04/06
CRDT- 2018/04/20 06:00
PHST- 2018/04/20 06:00 [entrez]
PHST- 2018/04/20 06:00 [pubmed]
PHST- 2018/09/18 06:00 [medline]
PHST- 2018/04/06 00:00 [pmc-release]
AID - dddt-12-787 [pii]
AID - 10.2147/DDDT.S145339 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2018 Apr 6;12:787-794. doi: 10.2147/DDDT.S145339. 
      eCollection 2018.