Transl Clin Pharmacol.  2018 Mar;26(1):16-24. 10.12793/tcp.2018.26.1.16.

Pharmacokinetics of fixed-dose combination of rosuvastatin 20 mg and ezetimibe 10 mg compared to concurrent administration of individual tablets in healthy Korean subjects

• Hwang I
• Park SI
• Lee S
• Lee B
• Yu KS
• Jeon JY
• Kim MG

• KMID: 2420303
• DOI: http://doi.org/10.12793/tcp.2018.26.1.16

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.

Keyword

Rosuvastatin; Ezetimibe; Fixed-dose combination; Pharmacokinetics; Bioequivalence

MeSH Terms

Cross-Over Studies
Ezetimibe*
Healthy Volunteers
Mass Spectrometry
Pharmacokinetics*
Plasma
Rosuvastatin Calcium*
Tablets*
Therapeutic Equivalency
Ezetimibe
Rosuvastatin Calcium
Tablets

Figure

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  Figure 1 Patient disposition from screening to completion or withdrawal in the fixed-dose combination tablet of rosuvastatin 20 mg / ezetimibe 10 mg or coadministration of rosuvastatin 20 mg and ezetimibe 10 mg.

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  Figure 2 Mean ± SD plasma concentration-time profiles of rosuvastatin after a single oral administration of fixed dose combination tablet (rosuvastatin 20 mg / ezetimibe 10 mg) or coadministration of rosuvastatin 20 mg and ezetimibe 10 mg. FDC = fixed dose combination. (A) linear scale (B) semi-log scale.

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  Figure 3 Mean ± SD plasma concentration-time profiles of ezetimibe after a single oral administration of fixed dose combination tablet (rosuvastatin 20 mg / ezetimibe 10 mg) or coadministration of rosuvastatin 20 mg and ezetimibe 10 mg. FDC = fixed dose combination. (A) linear scale (B) semi-log scale.

• 

  Figure 4 Mean ± SD plasma concentration-time profiles of total ezetimibe after a single oral administration of fixed dose combination tablet (rosuvastatin 20 mg / ezetimibe 10 mg) or coadministration of rosuvastatin 20 mg and ezetimibe 10 mg. FDC = fixed dose combination. (A) linear scale (B) semi-log scale.

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  Figure 5 Individual concentration-time profile of rosuvastatin after a single oral administration of (A) fixed dose combination tablet (rosuvastatin 20 mg / ezetimibe 10 mg) and (B) coadministration of rosuvastatin 20 mg and ezetimibe 10 mg.

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  Figure 6 Individual concentration-time profile of ezetimibe after a single oral administration of (A) fixed dose combination tablet (rosuvastatin 20 mg / ezetimibe 10 mg) and (B) coadministration of rosuvastatin 20 mg and ezetimibe 10 mg.

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  Figure 7 Individual (A) Cmax and (B) AUClast of rosuvastatin, (C) Cmax and (D) AUClast of ezetimibe, (E) Cmax and (F) AUClast of total ezetimibe after a single oral administration of fixed dose combination tablet (rosuvastatin 20 mg / ezetimibe 10 mg) or coadministration of rosuvastatin 20 mg and ezetimibe 10 mg. FDC = fixed dose combination.

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