Comparison of Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan/Rosuvastatin with Concomitant Administration of Amlodipine/Losartan and Rosuvastatin in Healthy Volunteers.
Administration, Oral
Adult
Amlodipine
/ administration & dosage
Cross-Over Studies
Dose-Response Relationship, Drug
Drug Combinations
Drug Compounding
Healthy Volunteers
Humans
Losartan
/ administration & dosage
Male
Middle Aged
Rosuvastatin Calcium
/ administration & dosage
Tablets
/ administration & dosage
bioequivalence
dyslipidemia
fixed-dose combination
hypertension
loose combination
pharmacokinetics
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
09
2019
accepted:
29
01
2020
entrez:
29
2
2020
pubmed:
29
2
2020
medline:
6
1
2021
Statut:
epublish
Résumé
A fixed-dose combination (FDC) tablet formulation of amlodipine/losartan/rosuvastatin 5/100/20 mg was developed to improve medication compliance in patients with both hypertension and dyslipidemia. The comparative pharmacokinetic study was performed to compare the profile of an FDC tablet formulation of amlodipine/losartan/rosuvastatin with that of concomitant administration of a currently marketed FDC tablet of amlodipine/losartan with a rosuvastatin tablet. A randomized, open-label, single oral dose, two-way crossover study was conducted in 60 healthy subjects. Subjects were orally administered the FDC tablet of amlodipine/losartan/rosuvastatin and a loose combination (LC) of two tablets comprising an FDC of amlodipine/losartan and rosuvastatin. Blood samples were collected for up to 144 h post dose for pharmacokinetic evaluations. Plasma concentrations of amlodipine, losartan, EXP3174 (an active metabolite of losartan), and rosuvastatin were measured by using liquid chromatography-tandem mass spectrometry. The geometric mean ratio (GMR) and its 90% confidence interval (90% CI) in the FDC treatment to LC treatment for the area under the concentration-time curve from zero to the last quantifiable time point (AUC The GMR (90% CI) values of AUC We confirmed the pharmacokinetic equivalence of the FDC and LC treatments. This triple combination FDC formulation could be a clinically useful replacement for LC therapy.
Sections du résumé
BACKGROUND
BACKGROUND
A fixed-dose combination (FDC) tablet formulation of amlodipine/losartan/rosuvastatin 5/100/20 mg was developed to improve medication compliance in patients with both hypertension and dyslipidemia. The comparative pharmacokinetic study was performed to compare the profile of an FDC tablet formulation of amlodipine/losartan/rosuvastatin with that of concomitant administration of a currently marketed FDC tablet of amlodipine/losartan with a rosuvastatin tablet.
SUBJECTS AND METHODS
METHODS
A randomized, open-label, single oral dose, two-way crossover study was conducted in 60 healthy subjects. Subjects were orally administered the FDC tablet of amlodipine/losartan/rosuvastatin and a loose combination (LC) of two tablets comprising an FDC of amlodipine/losartan and rosuvastatin. Blood samples were collected for up to 144 h post dose for pharmacokinetic evaluations. Plasma concentrations of amlodipine, losartan, EXP3174 (an active metabolite of losartan), and rosuvastatin were measured by using liquid chromatography-tandem mass spectrometry. The geometric mean ratio (GMR) and its 90% confidence interval (90% CI) in the FDC treatment to LC treatment for the area under the concentration-time curve from zero to the last quantifiable time point (AUC
RESULTS
RESULTS
The GMR (90% CI) values of AUC
CONCLUSION
CONCLUSIONS
We confirmed the pharmacokinetic equivalence of the FDC and LC treatments. This triple combination FDC formulation could be a clinically useful replacement for LC therapy.
Identifiants
pubmed: 32109991
doi: 10.2147/DDDT.S233014
pii: 233014
pmc: PMC7036667
doi:
Substances chimiques
Drug Combinations
0
Tablets
0
Amlodipine
1J444QC288
Rosuvastatin Calcium
83MVU38M7Q
Losartan
JMS50MPO89
Types de publication
Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
661-668Informations de copyright
© 2020 Yoon et al.
Déclaration de conflit d'intérêts
Jin-A Jung and Yong-Il Kim are both employees at Hanmi Pharm. Co., Ltd., Seoul, Republic of Korea. All authors declare no other conflicts of interest regarding the publication of this manuscript.
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