Transl Clin Pharmacol.  2017 Dec;25(4):202-208. 10.12793/tcp.2017.25.4.202.

Pharmacokinetic drug interaction between atorvastatin and ezetimibe in healthy Korean volunteers

• Park J
• Kim CO
• Jin BH
• Yang S
• Park MS
• Hong T

• KMID: 2407003
• DOI: http://doi.org/10.12793/tcp.2017.25.4.202

Abstract

Atorvastatin and ezetimibe are frequently co-administered to treat patients with dyslipidemia for the purpose of low-density lipoprotein cholesterol control. However, pharmacokinetic (PK) drug interaction between atorvastatin and ezetimibe has not been evaluated in Korean population. The aim of this study was to investigate PK drug interaction between two drugs in healthy Korean volunteers. An open-label, randomized, multiple-dose, three-treatment, three-period, Williams design crossover study was conducted in 36 healthy male subjects. During each period, the subjects received one of the following three treatments for seven days: atorvastatin 40 mg, ezetimibe 10 mg, or a combination of both. Blood samples were collected up to 96 h after dosing, and PK parameters of atorvastatin, 2-hydroxyatorvastatin, total ezetimibe (free ezetimibe + ezetimibe-glucuronide), and free ezetimibe were estimated by non-compartmental analysis in 32 subjects who completed the study. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of the maximum plasma concentration (C(max,ss)) and the area under the curve within a dosing interval at steady state (AUC(Ï„,ss)) of atorvastatin when administered with and without ezetimibe were 1.1087 (0.9799-1.2544) and 1.1154 (1.0079-1.2344), respectively. The corresponding values for total ezetimibe were 1.0005 (0.9227-1.0849) and 1.0176 (0.9465-1.0941). There was no clinically significant change in safety assessment related to either atorvastatin or ezetimibe. Co-administration of atorvastatin and ezetimibe showed similar PK and safety profile compared with each drug alone. The PK interaction between two drugs was not clinically significant in healthy Korean volunteers.

Keyword

Atorvastatin; Ezetimibe; Pharmacokinetics; Drug interaction

MeSH Terms

Atorvastatin Calcium*
Cholesterol
Cross-Over Studies
Drug Interactions*
Dyslipidemias
Ezetimibe*
Humans
Lipoproteins
Male
Pharmacokinetics
Plasma
Volunteers*
Atorvastatin Calcium
Cholesterol
Ezetimibe
Lipoproteins

Figure

• 

  Figure 1 Study design; treatment A, atorvastatin 40 mg once daily for seven days; treatment B, ezetimibe 10 mg once daily for seven days; treatment C, co-administration of atorvastatin 40 mg and ezetimibe 10 mg once daily for seven days.

• 

  Figure 2 Plasma concentration-time profiles of atorvastatin with or without ezetimibe at steady state plotted using (a) linear and (b) log-linear scales, and of 2-hydroxyatorvastatin (c) linear and (d) log-linear scales.

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  Figure 3 Plasma concentration-time profiles of total ezetimibe with or without atorvastatin at steady state plotted using (a) linear and (b) log-linear scales, and of free ezetimibe (c) linear and (d) log-linear scales.

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