Pharmacokinetics of fixed-dose combination of rosuvastatin 20 mg and ezetimibe 10 mg compared to concurrent administration of individual tablets in healthy Korean subjects
10.12793/tcp.2018.26.1.16
- Author:
Inyoung HWANG
1
;
Sang In PARK
;
SeungHwan LEE
;
BackHwan LEE
;
Kyung Sang YU
;
Ji Young JEON
;
Min Gul KIM
Author Information
1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Rosuvastatin;
Ezetimibe;
Fixed-dose combination;
Pharmacokinetics;
Bioequivalence
- MeSH:
Cross-Over Studies;
Ezetimibe;
Healthy Volunteers;
Mass Spectrometry;
Pharmacokinetics;
Plasma;
Rosuvastatin Calcium;
Tablets;
Therapeutic Equivalency
- From:Translational and Clinical Pharmacology
2018;26(1):16-24
- CountryRepublic of Korea
- Language:English
-
Abstract:
This study aimed to compare the pharmacokinetics of fixed-dose combination (FDC) tablet of rosuvastatin 20 mg/ezetimibe 10 mg with that of concurrent administration of individual rosuvastatin 20 mg tablet and ezetimibe 10 mg tablet in healthy subjects. A randomized, open label, single-dose, two-way crossover study was conducted. Subjects randomly received test formulation (FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg) or reference formulation (co-administration of rosuvastatin 20 mg tablet and ezetimibe 10 mg tablet). After 2 weeks of washout, subjects received the other treatment. Blood samples were collected up to 72 hours post-dose in each period. Plasma concentrations of rosuvastatin, ezetimibe and total ezetimibe (ezetimibe + ezetimibe glucuronide) were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The geometric mean ratio (GMR) of Cmax and AUClast (90% confidence interval, CI) for rosuvastatin was 1.036 (0.979–1.096) and 1.024 (0.981–1.070), respectively. The corresponding values for ezetimibe were 0.963 (0.888–1.043) and 1.021 (0.969–1.074), respectively. The corresponding values for total ezetimibe were 0.886 (0.835–0.940) and 0.983 (0.946–1.022), respectively. FDC tablet containing rosuvastatin 20 mg and ezetimibe 10 mg is bioequivalent to the co-administration of commercially available individual tablets of rosuvastatin and ezetimibe as GMR with 90% CI of Cmax and AUClast of rosuvastatin, ezetimibe and total ezetimibe were contained within conventionally accepted bioequivalence criteria.
